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Tumour microenvironment: a non-negligible driver for epithelial−mesenchymal transition in colorectal cancer

Published online by Cambridge University Press:  11 November 2021

Lei Han ,
Shuyi Wang ,
Chen Wei ,
Yan Fang ,
Sihao Huang ,
Tailang Yin ,
Bin Xiong  and
Chaogang Yang Open the ORCID record for Chaogang Yang [Opens in a new window]
Lei Han
Affiliation:
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan430071, China Hubei Key Laboratory of Tumour Biological Behaviours, Wuhan430071, China Hubei Cancer Clinical Study Centre, Wuhan430071, China The Clinical Medical Research Centre of Peritoneal Cancer of Wuhan, Wuhan430071, China
Shuyi Wang
Affiliation:
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan430071, China Hubei Key Laboratory of Tumour Biological Behaviours, Wuhan430071, China Hubei Cancer Clinical Study Centre, Wuhan430071, China The Clinical Medical Research Centre of Peritoneal Cancer of Wuhan, Wuhan430071, China
Chen Wei
Affiliation:
Department of Internal Medicine, Affiliated Tumour Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou450008, China
Yan Fang
Affiliation:
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan430071, China Hubei Key Laboratory of Tumour Biological Behaviours, Wuhan430071, China Hubei Cancer Clinical Study Centre, Wuhan430071, China The Clinical Medical Research Centre of Peritoneal Cancer of Wuhan, Wuhan430071, China
Sihao Huang
Affiliation:
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan430071, China Hubei Key Laboratory of Tumour Biological Behaviours, Wuhan430071, China Hubei Cancer Clinical Study Centre, Wuhan430071, China The Clinical Medical Research Centre of Peritoneal Cancer of Wuhan, Wuhan430071, China
Tailang Yin*
Affiliation:
Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan430060, China
Bin Xiong*
Affiliation:
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan430071, China Hubei Key Laboratory of Tumour Biological Behaviours, Wuhan430071, China Hubei Cancer Clinical Study Centre, Wuhan430071, China The Clinical Medical Research Centre of Peritoneal Cancer of Wuhan, Wuhan430071, China
Chaogang Yang*
Affiliation:
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan430071, China Hubei Key Laboratory of Tumour Biological Behaviours, Wuhan430071, China Hubei Cancer Clinical Study Centre, Wuhan430071, China The Clinical Medical Research Centre of Peritoneal Cancer of Wuhan, Wuhan430071, China
*
Authors for correspondence: Chaogang Yang, Bin Xiong, Tailang Yin, E-mail: ycg@whu.edu.cn, binxiong1961@whu.edu.cn, reproductive@whu.edu.cn
Authors for correspondence: Chaogang Yang, Bin Xiong, Tailang Yin, E-mail: ycg@whu.edu.cn, binxiong1961@whu.edu.cn, reproductive@whu.edu.cn
Authors for correspondence: Chaogang Yang, Bin Xiong, Tailang Yin, E-mail: ycg@whu.edu.cn, binxiong1961@whu.edu.cn, reproductive@whu.edu.cn
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Abstract

Cancer remains the leading cause of death worldwide, and metastasis is still the major cause of treatment failure for cancer patients. Epithelial–mesenchymal transition (EMT) has been shown to play a critical role in the metastasis cascade of epithelium-derived carcinoma. Tumour microenvironment (TME) refers to the local tissue environment in which tumour cells produce and live, including not only tumour cells themselves, but also fibroblasts, immune and inflammatory cells, glial cells and other cells around them, as well as intercellular stroma, micro vessels and infiltrated biomolecules from the nearby areas, which has been proved to widely participate in the occurrence and progress of cancer. Emerging and accumulating studies indicate that, on one hand, mesenchymal cells in TME can establish ‘crosstalk’ with tumour cells to regulate their EMT programme; on the other, EMT-tumour cells can create a favourable environment for their own growth via educating stromal cells. Recently, our group has conducted a series of studies on the interaction between tumour-associated macrophages (TAMs) and colorectal cancer (CRC) cells in TME, confirming that the interaction between TAMs and CRC cells mediated by cytokines or exosomes can jointly promote the metastasis of CRC by regulating the EMT process of tumour cells and the M2-type polarisation process of TAMs. Herein, we present an overview to describe the current knowledge about EMT in cancer, summarise the important role of TME in EMT, and provide an update on the mechanisms of TME-induced EMT in CRC, aiming to provide new ideas for understanding and resisting tumour metastasis.

Keywords

Colorectal cancerepithelial–mesenchymal transitionTAMtumour microenvironment
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e16
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

References

Bray, F et al. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians 68, 394–424.Google ScholarPubMed
Hanahan, D and Weinberg, RA (2011) Hallmarks of cancer: the next generation. Cell 144, 646–674.CrossRefGoogle ScholarPubMed
Valastyan, S and Weinberg, RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275–292.CrossRefGoogle ScholarPubMed
Obenauf, AC and Massague, J (2015) Surviving at a distance: organ-specific metastasis. Trends in Cancer 1, 76–91.CrossRefGoogle Scholar
Lu, W and Kang, Y (2019) Epithelial-mesenchymal plasticity in cancer progression and metastasis. Developmental Cell 49, 361–374.CrossRefGoogle ScholarPubMed
Hui, L and Chen, Y (2015) Tumor microenvironment: sanctuary of the devil. Cancer Letters 368, 7–13.CrossRefGoogle ScholarPubMed
Wei, C et al. (2019) Crosstalk between cancer cells and tumor-associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis. Molecular Cancer 18, 64.CrossRefGoogle ScholarPubMed
Wei, C et al. (2019) M2 macrophages confer resistance to 5-fluorouracil in colorectal cancer through the activation of CCL22/PI3 K/AKT signaling. OncoTargets and Therapy 12, 3051–3063.CrossRefGoogle Scholar
Yang, C et al. (2019) Elevated CD163(+)/CD68(+) ratio at tumor invasive front is closely associated with aggressive phenotype and poor prognosis in colorectal cancer. International Journal of Biological Sciences 15, 984–998.CrossRefGoogle ScholarPubMed
Noy, R and Pollard, JW (2014) Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49–61.CrossRefGoogle ScholarPubMed
Lin, X et al. (2019) miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization. Journal of Hematology & Oncology 12, 20.CrossRefGoogle ScholarPubMed
Yang, C et al. (2021) Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis. Molecular Therapy 29, 2088–2107.CrossRefGoogle ScholarPubMed
Kalluri, R and Weinberg, RA (2009) The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation 119, 1420–1428.CrossRefGoogle ScholarPubMed
Lamouille, S, Xu, J and Derynck, R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nature Reviews Molecular Cell Biology 15, 178–196.CrossRefGoogle ScholarPubMed
Yang, J et al. (2020) Guidelines and definitions for research on epithelial-mesenchymal transition. Nature Reviews Molecular Cell Biology 21, 341–352.CrossRefGoogle ScholarPubMed
Nieto, MA et al. (2016) EMT: 2016. Cell 166, 21–45.CrossRefGoogle ScholarPubMed
De Craene, B and Berx, G (2013) Regulatory networks defining EMT during cancer initiation and progression. Nature Reviews Cancer 13, 97–110.CrossRefGoogle ScholarPubMed
Dongre, A and Weinberg, RA (2019) New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nature Reviews Molecular Cell Biology 20, 69–84.CrossRefGoogle ScholarPubMed
Pei, D et al. (2019) Mesenchymal-epithelial transition in development and reprogramming. Nature Cell Biology 21, 44–53.CrossRefGoogle ScholarPubMed
Pastushenko, I et al. (2018) Identification of the tumour transition states occurring during EMT. Nature 556, 463–468.CrossRefGoogle ScholarPubMed
Gupta, PB et al. (2019) Phenotypic plasticity: driver of cancer initiation, progression, and therapy resistance. Cell Stem Cell 24, 65–78.CrossRefGoogle ScholarPubMed
Ansieau, S et al. (2010) TWISTing an embryonic transcription factor into an oncoprotein. Oncogene 29, 3173–3184.CrossRefGoogle ScholarPubMed
Maestro, R et al. (1999) Twist is a potential oncogene that inhibits apoptosis. Genes & Development 13, 2207–2217.CrossRefGoogle ScholarPubMed
Valsesia-Wittmann, S et al. (2004) Oncogenic cooperation between H-twist and N-Myc overrides failsafe programs in cancer cells. Cancer Cell 6, 625–630.CrossRefGoogle ScholarPubMed
Puisieux, A, Brabletz, T and Caramel, J (2014) Oncogenic roles of EMT-inducing transcription factors. Nature Cell Biology 16, 488–494.CrossRefGoogle ScholarPubMed
Liu, Y et al. (2014) Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis. Nature Communications 5, 5660.CrossRefGoogle ScholarPubMed
Phillips, S et al. (2014) Cell-state transitions regulated by SLUG are critical for tissue regeneration and tumor initiation. Stem Cell Reports 2, 633–647.CrossRefGoogle ScholarPubMed
Krebs, AM et al. (2017) The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nature Cell Biology 19, 518–529.CrossRefGoogle ScholarPubMed
Morel, AP et al. (2012) EMT Inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice. PLoS Genetics 8, e1002723.CrossRefGoogle ScholarPubMed
Ni, T et al. (2016) Snail1-dependent p53 repression regulates expansion and activity of tumour-initiating cells in breast cancer. Nature Cell Biology 18, 1221–1232.CrossRefGoogle ScholarPubMed
Wilson, MM et al. (2020) Emerging mechanisms by which EMT programs control stemness. Trends in Cancer 6, 775–780.CrossRefGoogle ScholarPubMed
Shibue, T and Weinberg, RA (2017) EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nature Reviews. Clinical Oncology 14, 611–629.CrossRefGoogle ScholarPubMed
Pradella, D et al. (2017) EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression. Molecular Cancer 16, 8.CrossRefGoogle ScholarPubMed
Lambert, AW and Weinberg, RA (2021) Linking EMT programmes to normal and neoplastic epithelial stem cells. Nature Reviews Cancer 21, 325–338.CrossRefGoogle ScholarPubMed
Scheel, C and Weinberg, RA (2012) Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Seminars in Cancer Biology 22, 396–403.CrossRefGoogle ScholarPubMed
Zheng, X et al. (2021) Communication between epithelial-mesenchymal plasticity and cancer stem cells: new insights into cancer progression. Frontiers in Oncology 11, 617597.CrossRefGoogle ScholarPubMed
Jayachandran, A, Dhungel, B and Steel, JC (2016) Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma. Journal of Hematology & Oncology 9, 74.CrossRefGoogle ScholarPubMed
Tanabe, S et al. (2020) Interplay of EMT and CSC in cancer and the potential therapeutic strategies. Frontiers in Pharmacology 11, 904.CrossRefGoogle ScholarPubMed
Wang, Z et al. (2011) Pancreatic cancer: understanding and overcoming chemoresistance. Nature Reviews, Gastroenterology & Hepatology 8, 27–33.CrossRefGoogle ScholarPubMed
Ramesh, V, Brabletz, T and Ceppi, P (2020) Targeting EMT in cancer with repurposed metabolic inhibitors. Trends in Cancer 6, 942–950.CrossRefGoogle ScholarPubMed
Cao, G et al. (2021) FHL3 Contributes to EMT and chemotherapy resistance through up-regulation of slug and activation of TGFbeta/Smad-independent pathways in gastric cancer. Frontiers in Oncology 11, 649029.CrossRefGoogle ScholarPubMed
Wrzesinski, SH, Wan, YY and Flavell, RA (2007) Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clinical Cancer Research 13, 5262–5270.CrossRefGoogle ScholarPubMed
Kudo-Saito, C et al. (2013) CCL2 Is critical for immunosuppression to promote cancer metastasis. Clinical & Experimental Metastasis 30, 393–405.CrossRefGoogle ScholarPubMed
Dongre, A et al. (2017) Epithelial-to-mesenchymal transition contributes to immunosuppression in breast carcinomas. Cancer Research 77, 3982–3989.CrossRefGoogle ScholarPubMed
Aiello, NM et al. (2017) Upholding a role for EMT in pancreatic cancer metastasis. Nature 547, E7–E8.CrossRefGoogle ScholarPubMed
Ye, X et al. (2017) Upholding a role for EMT in breast cancer metastasis. Nature 547, E1–E3.CrossRefGoogle ScholarPubMed
Zhong, Y et al. (2021) Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc. Signal Transduct Target Ther 6, 240.CrossRefGoogle ScholarPubMed
Spaderna, S et al. (2008) The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Research 68, 537–544.CrossRefGoogle ScholarPubMed
Yang, J et al. (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117, 927–939.CrossRefGoogle ScholarPubMed
Tran, HD et al. (2014) Transient SNAIL1 expression is necessary for metastatic competence in breast cancer. Cancer Research 74, 6330–6340.CrossRefGoogle ScholarPubMed
Ocana, OH et al. (2012) Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22, 709–724.CrossRefGoogle ScholarPubMed
Hanahan, D and Coussens, LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21, 309–322.CrossRefGoogle ScholarPubMed
Fan, QM et al. (2014) Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Letters 352, 160–168.CrossRefGoogle ScholarPubMed
Yu, Y et al. (2014) Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-beta signalling. British Journal of Cancer 110, 724–732.CrossRefGoogle ScholarPubMed
Pistore, C et al. (2017) DNA Methylation variations are required for epithelial-to-mesenchymal transition induced by cancer-associated fibroblasts in prostate cancer cells. Oncogene 36, 5551–5566.CrossRefGoogle ScholarPubMed
Qian, BZ and Pollard, JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39–51.CrossRefGoogle ScholarPubMed
Su, S et al. (2014) A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 25, 605–620.CrossRefGoogle ScholarPubMed
Che, D et al. (2017) Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE2/beta-catenin signalling pathway. Molecular Immunology 90, 197–210.CrossRefGoogle ScholarPubMed
Sakuma, K, Aoki, M and Kannagi, R (2012) Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition. Proceedings of the National Academy of Sciences of the United States of America 109, 7776–7781.CrossRefGoogle ScholarPubMed
Strutz, F et al. (2002) Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation. Kidney International 61, 1714–1728.CrossRefGoogle ScholarPubMed
Steinway, SN et al. (2014) Network modeling of TGFbeta signaling in hepatocellular carcinoma epithelial-to-mesenchymal transition reveals joint sonic hedgehog and Wnt pathway activation. Cancer Research 74, 5963–5977.CrossRefGoogle ScholarPubMed
Jung, HY, Fattet, L and Yang, J (2015) Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis. Clinical Cancer Research 21, 962–968.CrossRefGoogle Scholar
Akalay, I et al. (2013) EMT impairs breast carcinoma cell susceptibility to CTL-mediated lysis through autophagy induction. Autophagy 9, 1104–1106.CrossRefGoogle ScholarPubMed
Hsu, DS et al. (2014) Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages. Cancer Cell 26, 534–548.CrossRefGoogle ScholarPubMed
Dominguez, C, David, JM and Palena, C (2017) Epithelial-mesenchymal transition and inflammation at the site of the primary tumor. Seminars in Cancer Biology 47, 177–184.CrossRefGoogle Scholar
Fernando, RI et al. (2011) IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. Cancer Research 71, 5296–5306.CrossRefGoogle Scholar
Erin, N et al. (2020) Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy 53, 100715.CrossRefGoogle ScholarPubMed
Cassetta, L and Pollard, JW (2020) Tumor-associated macrophages. Current Biology 30, R246–RR48.CrossRefGoogle ScholarPubMed
Solinas, G et al. (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. Journal of Leukocyte Biology 86, 1065–1073.CrossRefGoogle ScholarPubMed
Biswas, SK and Mantovani, A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nature Immunology 11, 889–896.CrossRefGoogle ScholarPubMed
Lee, CC et al. (2018) Macrophage-secreted interleukin-35 regulates cancer cell plasticity to facilitate metastatic colonization. Nature Communications 9, 3763.CrossRefGoogle ScholarPubMed
Mantovani, A et al. (2017) Tumour-associated macrophages as treatment targets in oncology. Nature Reviews. Clinical Oncology 14, 399–416.CrossRefGoogle ScholarPubMed
Komohara, Y et al. (2016) Tumor-associated macrophages: potential therapeutic targets for anti-cancer therapy. Advanced Drug Delivery Reviews 99, 180–185.CrossRefGoogle ScholarPubMed
Steidl, C et al. (2010) Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. New England Journal of Medicine 362, 875–885.CrossRefGoogle ScholarPubMed
Abdou, AG et al. (2013) The prognostic role of tumor-associated macrophages and dendritic cells in classic Hodgkin's lymphoma. Journal of Environmental Pathology Toxicology and Oncology 32, 289–305.CrossRefGoogle ScholarPubMed
DeNardo, DG and Ruffell, B (2019) Macrophages as regulators of tumour immunity and immunotherapy. Nature Reviews Immunology 19, 369–382.CrossRefGoogle ScholarPubMed
De Palma, M, Nassiri, S and Cianciaruso, C (2019) Macrophage interference on chemotherapy. Nature Cell Biology 21, 411–412.CrossRefGoogle ScholarPubMed
Mantovani, A and Allavena, P (2015) The interaction of anticancer therapies with tumor-associated macrophages. Journal of Experimental Medicine 212, 435–445.CrossRefGoogle ScholarPubMed
Vitale, I et al. (2019) Macrophages and metabolism in the tumor microenvironment. Cell Metabolism 30, 36–50.CrossRefGoogle ScholarPubMed
Yang, Z et al. (2020) The prognostic and clinicopathological value of tumor-associated macrophages in patients with colorectal cancer: a systematic review and meta-analysis. International Journal of Colorectal Disease 35, 1651–1661.CrossRefGoogle ScholarPubMed
Vinnakota, K et al. (2017) M2-like macrophages induce colon cancer cell invasion via matrix metalloproteinases. Journal of Cellular Physiology 232, 3468–3480.CrossRefGoogle ScholarPubMed
Li, S et al. (2018) Tumor-associated macrophages remodeling EMT and predicting survival in colorectal carcinoma. Oncoimmunology 7, e1380765.CrossRefGoogle ScholarPubMed
Inagaki, K et al. (2021) Role of tumor-associated macrophages at the invasive front in human colorectal cancer progression. Cancer Science 112, 2692–2704.CrossRefGoogle Scholar
Zhong, Q et al. (2020) CPEB3 inhibits epithelial-mesenchymal transition by disrupting the crosstalk between colorectal cancer cells and tumor-associated macrophages via IL-6R/STAT3 signaling. Journal of Experimental & Clinical Cancer Research: CR 39, 132.CrossRefGoogle ScholarPubMed
Zhang, T et al. (2019) Interaction with tumour-associated macrophages promotes PRL3induced invasion of colorectal cancer cells via MAPK pathway induced EMT and NFkappaB signaling induced angiogenesis. Oncology Reports 41, 2790–2802.Google Scholar
Santiago, L et al. (2020) Extracellular granzyme A promotes colorectal cancer development by enhancing gut inflammation. Cell Reports 32, 107847.CrossRefGoogle ScholarPubMed
Wan, G et al. (2018) Intestinal dysbacteriosis activates tumor-associated macrophages to promote epithelial-mesenchymal transition of colorectal cancer. Innate Immunity 24, 480–489.CrossRefGoogle ScholarPubMed
Cai, J et al. (2019) Tumor-associated macrophages derived TGF-beta induced epithelial to mesenchymal transition in colorectal cancer cells through Smad2,3-4/snail signaling pathway. Cancer Research and Treatment: Official Journal of Korean Cancer Association 51, 252–266.CrossRefGoogle ScholarPubMed
Wang, D et al. (2020) Exosome-encapsulated miRNAs contribute to CXCL12/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Letters 474, 36–52.CrossRefGoogle ScholarPubMed
Wu, J et al. (2019) The malignant role of exosomes in the communication among colorectal cancer cell, macrophage and microbiome. Carcinogenesis 40, 601–610.Google ScholarPubMed
Zhang, J et al. (2021) LncRNA HLA-F-AS1 promotes colorectal cancer metastasis by inducing PFN1 in colorectal cancer-derived extracellular vesicles and mediating macrophage polarization. Cancer Gene Therapy.Google ScholarPubMed
Liang, ZX et al. (2019) LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization. Cell Death & Disease 10, 829.CrossRefGoogle ScholarPubMed
Cho, U et al. (2018) Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer cells through NF-kappaB activation. Molecular Carcinogenesis 57, 235–242.CrossRefGoogle ScholarPubMed
Guo, L et al. (2019) Induction of breast cancer stem cells by M1 macrophages through Lin-28B-let-7-HMGA2 axis. Cancer Letters 452, 213–225.CrossRefGoogle ScholarPubMed
Sahai, E et al. (2020) A framework for advancing our understanding of cancer-associated fibroblasts. Nature Reviews Cancer 20, 174–186.CrossRefGoogle ScholarPubMed
Prakash, J (2016) Cancer-associated fibroblasts: perspectives in cancer therapy. Trends in Cancer 2, 277–279.CrossRefGoogle ScholarPubMed
Chen, X and Song, E (2019) Turning foes to friends: targeting cancer-associated fibroblasts. Nature Reviews. Drug Discovery 18, 99–115.CrossRefGoogle ScholarPubMed
Tommelein, J et al. (2015) Cancer-associated fibroblasts connect metastasis-promoting communication in colorectal cancer. Frontiers in Oncology 5, 63.CrossRefGoogle ScholarPubMed
Herrera, M et al. (2013) Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer Science 104, 437–444.CrossRefGoogle ScholarPubMed
Jahangiri, B et al. (2019) Cancer-associated fibroblasts enhance cell proliferation and metastasis of colorectal cancer SW480 cells by provoking long noncoding RNA UCA1. Journal of Cell Communication and Signaling 13, 53–64.CrossRefGoogle ScholarPubMed
Karagiannis, GS et al. (2012) Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Molecular Cancer Research 10, 1403–1418.CrossRefGoogle ScholarPubMed
Bauer, J et al. (2020) Increased stiffness of the tumor microenvironment in colon cancer stimulates cancer-associated fibroblast-mediated prometastatic activin A signaling. Scientific Reports 10, 50.CrossRefGoogle ScholarPubMed
Liu, R et al. (2013) FGFR4 Promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer. Cancer Research 73, 5926–5935.CrossRefGoogle ScholarPubMed
Hu, JL et al. (2019) CAFS secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Molecular Cancer 18, 91.CrossRefGoogle ScholarPubMed
Zhou, L et al. (2021) Exosomal LncRNA LINC00659 transferred from cancer-associated fibroblasts promotes colorectal cancer cell progression via miR-342-3p/ANXA2 axis. Journal of Translational Medicine 19, 8.CrossRefGoogle ScholarPubMed
Ganguly, D et al. (2020) Cancer-Associated fibroblasts: versatile players in the tumor microenvironment. Cancers 12, 9.CrossRefGoogle ScholarPubMed
Ohlund, D, Elyada, E and Tuveson, D (2014) Fibroblast heterogeneity in the cancer wound. Journal of Experimental Medicine 211, 1503–1523.CrossRefGoogle ScholarPubMed
Mosa, MH et al. (2020) A Wnt-induced phenotypic switch in cancer-associated fibroblasts inhibits EMT in colorectal cancer. Cancer Research 80, 5569–5582.CrossRefGoogle ScholarPubMed
Cao, H et al. (2021) A 3D physio-mimetic interpenetrating network-based platform to decode the pro and anti-tumorigenic properties of cancer-associated fibroblasts. Acta Biomaterialia 132, 448–460.CrossRefGoogle ScholarPubMed
Li, H et al. (2017) Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors. Nature Genetics 49, 708–718.CrossRefGoogle ScholarPubMed
Vellinga, TT et al. (2016) Collagen-rich stroma in aggressive colon tumors induces mesenchymal gene expression and tumor cell invasion. Oncogene 35, 5263–5271.CrossRefGoogle ScholarPubMed
Hu, X et al. (2018) ITGAE Defines CD8 + tumor-infiltrating lymphocytes predicting a better prognostic survival in colorectal cancer. EBioMedicine 35, 178–188.CrossRefGoogle ScholarPubMed
Kan, JY et al. (2015) Chemokine (C-C motif) ligand 5 is involved in tumor-associated dendritic cell-mediated colon cancer progression through non-coding RNA MALAT-1. Journal of Cellular Physiology 230, 1883–1894.CrossRefGoogle Scholar
Hsu, YL et al. (2018) Interaction between tumor-associated dendritic cells and colon cancer cells contributes to tumor progression via CXCL1. International Journal of Molecular Sciences 19, 2427.CrossRefGoogle ScholarPubMed
Templeton, AJ et al. (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Journal of the National Cancer Institute 106, dju124.CrossRefGoogle ScholarPubMed
Fridlender, ZG et al. (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16, 183–194.CrossRefGoogle ScholarPubMed
Mizuno, R et al. (2019) The role of tumor-associated neutrophils in colorectal cancer. International Journal of Molecular Sciences 20, 529.CrossRefGoogle ScholarPubMed
Mohan, V, Das, A and Sagi, I (2020) Emerging roles of ECM remodeling processes in cancer. Seminars in Cancer Biology 62, 192–200.CrossRefGoogle ScholarPubMed
Bulle, A and Lim, KH (2020) Beyond just a tight fortress: contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer. Signal Transduct Target Ther 5, 249.CrossRefGoogle ScholarPubMed
Kirkland, SC (2009) Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells. British Journal of Cancer 101, 320–326.CrossRefGoogle ScholarPubMed
Mao, L et al. (2021) Decorin deficiency promotes epithelial-mesenchymal transition and colon cancer metastasis. Matrix Biology 95, 1–14.CrossRefGoogle ScholarPubMed
Plantureux, L et al. (2020) The interaction of platelets with colorectal cancer cells inhibits tumor growth but promotes metastasis. Cancer Research 80, 291–303.CrossRefGoogle ScholarPubMed
Corbet, C et al. (2020) TGFbeta2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nature Communications 11, 454.CrossRefGoogle ScholarPubMed
Choi, BJ et al. (2017) Hypoxia induces epithelial-mesenchymal transition in colorectal cancer cells through ubiquitin-specific protease 47-mediated stabilization of snail: a potential role of Sox9. Scientific Reports 7, 15918.CrossRefGoogle ScholarPubMed
Papiewska-Pajak, I et al. (2021) Snail overexpression alters the microRNA content of extracellular vesicles released from HT29 colorectal cancer cells and activates Pro-inflammatory state in vivo. Cancers 13, 172.CrossRefGoogle ScholarPubMed
Druzhkova, I et al. (2020) Expression of EMT-related genes in hybrid E/M colorectal cancer cells determines fibroblast activation and collagen remodeling. International Journal of Molecular Sciences 21, 8119.CrossRefGoogle ScholarPubMed
Bota-Rabassedas, N et al. (2021) Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity. Cell Reports 35, 109009.CrossRefGoogle ScholarPubMed
Fiori, ME et al. (2019) Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance. Molecular Cancer 18, 70.CrossRefGoogle Scholar
Scagliotti, GV, Novello, S and von Pawel, J (2013) The emerging role of MET/HGF inhibitors in oncology. Cancer Treatment Reviews 39, 793–801.CrossRefGoogle ScholarPubMed
Neuzillet, C et al. (2015) Targeting the TGFbeta pathway for cancer therapy. Pharmacology & Therapeutics 147, 22–31.CrossRefGoogle ScholarPubMed
Kim, SL et al. (2020) A novel HDAC1 inhibitor, CBUD1001, exerts anticancer effects by modulating the apoptosis and EMT of colorectal cancer cells. International Journal of Oncology 57, 1027–1038.Google ScholarPubMed