Stromal-Modulated Epithelial-to-Mesenchymal Transition in Cancer Cells

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2023 Nov 25

PMID 38002286

Authors

Huda I Atiya

Grace Gorecki

Geyon L Garcia

Leonard G Frisbie

Roja Baruwal

Lan Coffman

Affiliations

Soon will be listed here.

Abstract

The ability of cancer cells to detach from the primary site and metastasize is the main cause of cancer- related death among all cancer types. Epithelial-to-mesenchymal transition (EMT) is the first event of the metastatic cascade, resulting in the loss of cell-cell adhesion and the acquisition of motile and stem-like phenotypes. A critical modulator of EMT in cancer cells is the stromal tumor microenvironment (TME), which can promote the acquisition of a mesenchymal phenotype through direct interaction with cancer cells or changes to the broader microenvironment. In this review, we will explore the role of stromal cells in modulating cancer cell EMT, with particular emphasis on the function of mesenchymal stromal/stem cells (MSCs) through the activation of EMT-inducing pathways, extra cellular matrix (ECM) remodeling, immune cell alteration, and metabolic rewiring.

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References

Koukourakis M, Giatromanolaki A, Harris A, Sivridis E . Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res. 2006; 66(2):632-7. DOI: 10.1158/0008-5472.CAN-05-3260. View

Yang L, Zhang F, Wang X, Tsai Y, Chuang K, Keng P . A FASN-TGF-β1-FASN regulatory loop contributes to high EMT/metastatic potential of cisplatin-resistant non-small cell lung cancer. Oncotarget. 2016; 7(34):55543-55554. PMC: 5342435. DOI: 10.18632/oncotarget.10837. View

Fallarino F, Grohmann U, You S, McGrath B, Cavener D, Vacca C . The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol. 2006; 176(11):6752-61. DOI: 10.4049/jimmunol.176.11.6752. View

Frisbie L, Buckanovich R, Coffman L . Carcinoma-Associated Mesenchymal Stem/Stromal Cells: Architects of the Pro-tumorigenic Tumor Microenvironment. Stem Cells. 2022; 40(8):705-715. PMC: 9406606. DOI: 10.1093/stmcls/sxac036. View

Kim B, Ahn D, Kang N, Yeo C, Kim Y, Lee K . TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci Rep. 2020; 10(1):10597. PMC: 7326979. DOI: 10.1038/s41598-020-67325-7. View

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S . Human ovarian carcinoma–associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Invest. 2011; 121(8):3206-19. PMC: 3148732. DOI: 10.1172/JCI45273. View

Jin Y, Bian S, Wang H, Mo J, Fei H, Li L . CRMP2 derived from cancer associated fibroblasts facilitates progression of ovarian cancer via HIF-1α-glycolysis signaling pathway. Cell Death Dis. 2022; 13(8):675. PMC: 9352901. DOI: 10.1038/s41419-022-05129-5. View

Rodriguez-Garcia A, Samso P, Fontova P, Simon-Molas H, Manzano A, Castano E . TGF-β1 targets Smad, p38 MAPK, and PI3K/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells. FEBS J. 2017; 284(20):3437-3454. DOI: 10.1111/febs.14201. View

10.

Radisky E, Radisky D . Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J Mammary Gland Biol Neoplasia. 2010; 15(2):201-12. PMC: 2886087. DOI: 10.1007/s10911-010-9177-x. View

11.

Wang C, Shao L, Pan C, Ye J, Ding Z, Wu J . Elevated level of mitochondrial reactive oxygen species via fatty acid β-oxidation in cancer stem cells promotes cancer metastasis by inducing epithelial-mesenchymal transition. Stem Cell Res Ther. 2019; 10(1):175. PMC: 6567550. DOI: 10.1186/s13287-019-1265-2. View

12.

Frose J, Chen M, Hebron K, Reinhardt F, Hajal C, Zijlstra A . Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling. Cell Rep. 2018; 24(4):962-972. PMC: 6181240. DOI: 10.1016/j.celrep.2018.06.092. View

13.

Sympson C, Bissell M, Werb Z . Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1. Semin Cancer Biol. 1995; 6(3):159-63. PMC: 3815639. DOI: 10.1006/scbi.1995.0022. View

14.

Sousa C, Biancur D, Wang X, Halbrook C, Sherman M, Zhang L . Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 2016; 536(7617):479-83. PMC: 5228623. DOI: 10.1038/nature19084. View

15.

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

16.

Gordon J, Evans M, Ghule P, Lee K, Vacek P, Sprague B . Identification of molecularly unique tumor-associated mesenchymal stromal cells in breast cancer patients. PLoS One. 2023; 18(3):e0282473. PMC: 10027225. DOI: 10.1371/journal.pone.0282473. View

17.

Liu M, Quek L, Sultani G, Turner N . Epithelial-mesenchymal transition induction is associated with augmented glucose uptake and lactate production in pancreatic ductal adenocarcinoma. Cancer Metab. 2016; 4:19. PMC: 5066287. DOI: 10.1186/s40170-016-0160-x. View

18.

Andreucci E, Peppicelli S, Ruzzolini J, Bianchini F, Biagioni A, Papucci L . The acidic tumor microenvironment drives a stem-like phenotype in melanoma cells. J Mol Med (Berl). 2020; 98(10):1431-1446. PMC: 7525286. DOI: 10.1007/s00109-020-01959-y. View

19.

Balkwill F, Montfort A, Capasso M . B regulatory cells in cancer. Trends Immunol. 2012; 34(4):169-73. DOI: 10.1016/j.it.2012.10.007. View

20.

Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A . T cell apoptosis by tryptophan catabolism. Cell Death Differ. 2002; 9(10):1069-77. DOI: 10.1038/sj.cdd.4401073. View