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Erschienen in: Cancer and Metastasis Reviews 1/2022

03.01.2022 | Non-Thematic Review

Emerging roles of epithelial-mesenchymal plasticity in invasion-metastasis cascade and therapy resistance

verfasst von: Minal Garg

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1/2022

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Abstract

Strong association of cancer incidence and its progression with mortality highlights the need to decipher the cellular and molecular mechanisms that drive tumor cells to rapidly progress to metastatic disease and therapy resistance. Epithelial-mesenchymal plasticity (EMP) emerged as a key regulator of metastatic outgrowth. It allows neoplastic epithelial cells to delaminate from their neighbors either individually or collectively, traverse the extracellular matrix (ECM) barrier, enter into the circulation, and establish distal metastases. Plasticity between epithelial and mesenchymal states and the existence of hybrid epithelial/mesenchymal (E/M) phenotypes are increasingly being reported in different tumor contexts. Small subset of cancer cells with stemness called cancer stem cells (CSCs) exhibit plasticity, possess high tumorigenic potential, and contribute to high degree of tumoral heterogeneity. EMP characterized by the presence of dynamic intermediate states is reported to be influenced by (epi)genomic reprograming, growth factor signaling, inflammation, and low oxygen generated by tumor stromal microenvironment. EMP alters the genotypic and phenotypic characteristics of tumor cells/CSCs, disrupts tissue homeostasis, induces the reprogramming of angiogenic and immune recognition functions, and renders tumor cells to survive hostile microenvironments and resist therapy. The present review summarizes the roles of EMP in tumor invasion and metastasis and provides an update on therapeutic strategies to target the metastatic and refractory cancers.
Literatur
3.
Zurück zum Zitat Hass, R., von der Ohe, J., & Ungefroren, H. (2020). The intimate relationship among EMT MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to be exploited for therapeutic purposes. Cancers, 12, 3674.CrossRefPubMedCentral Hass, R., von der Ohe, J., & Ungefroren, H. (2020). The intimate relationship among EMT MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to be exploited for therapeutic purposes. Cancers, 12, 3674.CrossRefPubMedCentral
12.
Zurück zum Zitat Garg, M., & Singh, R. (2019). Epithelial-to-mesenchymal transition: Event and core associates in bladder cancer. Frontiers in Bioscience, 11, 150–165. PMID: 31136970.CrossRef Garg, M., & Singh, R. (2019). Epithelial-to-mesenchymal transition: Event and core associates in bladder cancer. Frontiers in Bioscience, 11, 150–165. PMID: 31136970.CrossRef
19.
Zurück zum Zitat Aiello, N. M., Maddipati, R., Norgard, R. J., Balli, D., Jinyang, Li., Yuan, S., et al. (2018). EMT subtype influences epithelial plasticity and mode of cell migration. Developmental Cell, 45(6), 681-695.e4.CrossRefPubMedPubMedCentral Aiello, N. M., Maddipati, R., Norgard, R. J., Balli, D., Jinyang, Li., Yuan, S., et al. (2018). EMT subtype influences epithelial plasticity and mode of cell migration. Developmental Cell, 45(6), 681-695.e4.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Godin, L., Balsat, C., Van Eycke, Y.-R., Allard, J., Royer, C., Remmelink, M., et al. (2020). A novel approach for quantifying cancer cells showing hybrid epithelial/mesenchymal states in large series of tissue samples: Towards a new prognostic marker. Cancers (Basel), 12(4), 906.CrossRefPubMedCentral Godin, L., Balsat, C., Van Eycke, Y.-R., Allard, J., Royer, C., Remmelink, M., et al. (2020). A novel approach for quantifying cancer cells showing hybrid epithelial/mesenchymal states in large series of tissue samples: Towards a new prognostic marker. Cancers (Basel), 12(4), 906.CrossRefPubMedCentral
40.
43.
Zurück zum Zitat Burman, D. R., Das, S., Das, C., & Bhattacharya, R. (2021). Alternative splicing modulates cancer aggressiveness: Role in EMT/metastasis and chemoresistance. Molecular Biology Reports, 48(1), 897–914.CrossRef Burman, D. R., Das, S., Das, C., & Bhattacharya, R. (2021). Alternative splicing modulates cancer aggressiveness: Role in EMT/metastasis and chemoresistance. Molecular Biology Reports, 48(1), 897–914.CrossRef
63.
Zurück zum Zitat Diepenbruck, M., Waldmeier, L., Ivanek, R., Berninger, P., Arnold, P., Van Nimwegen, E., et al. (2014). Tead2 expression levels control the subcellular distribution of Yap and Taz, zyxin expression and epithelial-mesenchymal transition. Journal of Cell Science, 127, 1523–1536. https://doi.org/10.1242/jcs.139865CrossRefPubMed Diepenbruck, M., Waldmeier, L., Ivanek, R., Berninger, P., Arnold, P., Van Nimwegen, E., et al. (2014). Tead2 expression levels control the subcellular distribution of Yap and Taz, zyxin expression and epithelial-mesenchymal transition. Journal of Cell Science, 127, 1523–1536. https://​doi.​org/​10.​1242/​jcs.​139865CrossRefPubMed
67.
Zurück zum Zitat Tata, P. R., Chow, R. D., Saladi, S. V., Tata, A., Konkimalla, A., Bara, A., et al. (2018). Developmental history provides a roadmap for the emergence of tumor plasticity. Dev Cell, 44, 679-693e5.CrossRefPubMedPubMedCentral Tata, P. R., Chow, R. D., Saladi, S. V., Tata, A., Konkimalla, A., Bara, A., et al. (2018). Developmental history provides a roadmap for the emergence of tumor plasticity. Dev Cell, 44, 679-693e5.CrossRefPubMedPubMedCentral
75.
Zurück zum Zitat Xiong, H. G., Li, H., Xiao, Y., Yang, Q. C., Yang, L. L., Chen, L., et al. (2019). Long noncoding RNA MYOSLID promotes invasion and metastasis by modulating the partial epithelial-mesenchymal transition program in head and neck squamous cell carcinoma. Journal of Experimental & Clinical Cancer Research, 38, 278. https://doi.org/10.1186/s13046-019-1254-4CrossRef Xiong, H. G., Li, H., Xiao, Y., Yang, Q. C., Yang, L. L., Chen, L., et al. (2019). Long noncoding RNA MYOSLID promotes invasion and metastasis by modulating the partial epithelial-mesenchymal transition program in head and neck squamous cell carcinoma. Journal of Experimental & Clinical Cancer Research, 38, 278. https://​doi.​org/​10.​1186/​s13046-019-1254-4CrossRef
79.
103.
109.
113.
Zurück zum Zitat Jiang, L., Xiao, L., Sugiura, H., Huang, X., Ali, A., Kuro-o, M., et al. (2015). Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition. Oncogene, 34(30), 3908–3916.CrossRefPubMed Jiang, L., Xiao, L., Sugiura, H., Huang, X., Ali, A., Kuro-o, M., et al. (2015). Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition. Oncogene, 34(30), 3908–3916.CrossRefPubMed
115.
Metadaten
Titel
Emerging roles of epithelial-mesenchymal plasticity in invasion-metastasis cascade and therapy resistance
verfasst von
Minal Garg
Publikationsdatum
03.01.2022
Verlag
Springer US
Erschienen in
Cancer and Metastasis Reviews / Ausgabe 1/2022
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-021-10003-5

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