Vydra, N.; Toma-Jonik, A.; Janus, P.; Mrowiec, K.; Stokowy, T.; Głowala-Kosińska, M.; Sojka, D.R.; Olbryt, M.; Widłak, W. An Increase in HSF1 Expression Directs Human Mammary Epithelial Cells toward a Mesenchymal Phenotype. Cancers2023, 15, 4965.
Vydra, N.; Toma-Jonik, A.; Janus, P.; Mrowiec, K.; Stokowy, T.; Głowala-Kosińska, M.; Sojka, D.R.; Olbryt, M.; Widłak, W. An Increase in HSF1 Expression Directs Human Mammary Epithelial Cells toward a Mesenchymal Phenotype. Cancers 2023, 15, 4965.
Vydra, N.; Toma-Jonik, A.; Janus, P.; Mrowiec, K.; Stokowy, T.; Głowala-Kosińska, M.; Sojka, D.R.; Olbryt, M.; Widłak, W. An Increase in HSF1 Expression Directs Human Mammary Epithelial Cells toward a Mesenchymal Phenotype. Cancers2023, 15, 4965.
Vydra, N.; Toma-Jonik, A.; Janus, P.; Mrowiec, K.; Stokowy, T.; Głowala-Kosińska, M.; Sojka, D.R.; Olbryt, M.; Widłak, W. An Increase in HSF1 Expression Directs Human Mammary Epithelial Cells toward a Mesenchymal Phenotype. Cancers 2023, 15, 4965.
Abstract
HSF1 is a well-known Heat Shock Protein expression regulator in response to stress. It also regulates processes important for growth, development, or tumorigenesis. Here, we studied the HSF1 influence on the phenotype of non-tumorigenic human mammary epithelial (MCF10A and MCF12A) and several triple-negative breast cancer cell lines. MCF10A and MCF12A differ by HSF1 levels, morphology, growth in the matrigel, expression of epithelial (CDH1) and mesenchymal (VIM) markers (MCF10A are epithelial cells, MCF12A resemble mesenchymal cells). HSF1 down-regulation led to reduced proliferation rate and spheroid formation in matrigel by MCF10A cells, while it did not affect the MCF12A proliferation but led to CDH1 up-regulation and the formation of better-organized spheroids. HSF1 overexpression in MCF10A resulted in reduced CDH1 and increased VIM expression, and the acquisition of elongated fibroblast-like morphology. The above results suggest that elevated levels of HSF1 may direct mammary epithelial cells toward a mesenchymal phenotype while lowering HSF1 could reverse the mesenchymal phenotype to an epithelial one. Therefore, HSF1 may be involved in the remodeling of mammary gland architecture over the female lifetime. Moreover, HSF1 levels positively correlated with the invasive phenotype of triple-negative breast cancer cells, and their growth was inhibited by the HSF1 inhibitor, DTHIB.
Biology and Life Sciences, Cell and Developmental Biology
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