Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial-Mesenchymal Plasticity

0555643 - BFÚ 2022 RIV CH eng J - Článek v odborném periodiku
Kvokačková, Barbora - Remsik, J. - Jolly, M. K. - Souček, Karel
Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial-Mesenchymal Plasticity.
Cancers (Basel). Roč. 13, č. 9 (2021), č. článku 2188. E-ISSN 2072-6694
Grant CEP: GA MZd(CZ) NV18-08-00245; GA ČR(CZ) GA20-22984S
Institucionální podpora: RVO:68081707
Klíčová slova: circulating tumor-cells * e-cadherin * stem-cells * prognostic value * down-regulation * metastatic colonization
Obor OECD: Oncology
Impakt faktor: 6.575, rok: 2021
Způsob publikování: Open access
https://www.mdpi.com/2072-6694/13/9/2188

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are considered critical events in the cancer progression. These programs are tightly connected with the development of metastasis-the lethal stage of the disease. Both EMT and MET shape the biology of unusually aggressive and heterogeneous triple-negative breast cancer (TNBC). In this review, we summarize the current knowledge of EMT/MET plasticity in the context of TNBC, with a special focus on drivers and mechanisms behind these processes.

Triple-negative breast cancer (TNBC) is a subtype of breast carcinoma known for its unusually aggressive behavior and poor clinical outcome. Besides the lack of molecular targets for therapy and profound intratumoral heterogeneity, the relatively quick overt metastatic spread remains a major obstacle in effective clinical management. The metastatic colonization of distant sites by primary tumor cells is affected by the microenvironment, epigenetic state of particular subclones, and numerous other factors. One of the most prominent processes contributing to the intratumoral heterogeneity is an epithelial-mesenchymal transition (EMT), an evolutionarily conserved developmental program frequently hijacked by tumor cells, strengthening their motile and invasive features. In response to various intrinsic and extrinsic stimuli, malignant cells can revert the EMT state through the mesenchymal-epithelial transition (MET), a process that is believed to be critical for the establishment of macrometastasis at secondary sites. Notably, cancer cells rarely undergo complete EMT and rather exist in a continuum of E/M intermediate states, preserving high levels of plasticity, as demonstrated in primary tumors and, ultimately, in circulating tumor cells, representing a simplified element of the metastatic cascade. In this review, we focus on cellular drivers underlying EMT/MET phenotypic plasticity and its detrimental consequences in the context of TNBC cancer.
Trvalý link: http://hdl.handle.net/11104/0330100