Vydra Natalia, Toma-Jonik Agnieszka, Janus Patryk, Mrowiec Katarzyna, Stokowy Tomasz, Głowala-Kosińska Magdalena, Sojka Damian Robert, Olbryt Magdalena, Widłak Wiesława
Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-102 Gliwice, Poland.
Scientific Computing Group, IT Division, University of Bergen, N-5008 Bergen, Norway.
Cancers (Basel). 2023 Oct 12;15(20):4965. doi: 10.3390/cancers15204965.
HSF1 is a well-known heat shock protein expression regulator in response to stress. It also regulates processes important for growth, development or tumorigenesis. 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 in terms of HSF1 levels, morphology, growth in Matrigel, expression of epithelial (CDH1) and mesenchymal (VIM) markers (MCF10A are epithelial cells; MCF12A resemble mesenchymal cells). HSF1 down-regulation led to a reduced proliferation rate and spheroid formation in Matrigel by MCF10A cells. However, it did not affect 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-mentioned results suggest that elevated levels of HSF1 may direct mammary epithelial cells toward a mesenchymal phenotype, while a lowering of 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.
HSF1是一种众所周知的对应激作出反应的热休克蛋白表达调节因子。它还调节对生长、发育或肿瘤发生很重要的过程。我们研究了HSF1对非致瘤性人乳腺上皮细胞（MCF10A和MCF12A）以及几种三阴性乳腺癌细胞系表型的影响。MCF10A和MCF12A在HSF1水平、形态、在基质胶中的生长、上皮（CDH1）和间充质（VIM）标志物的表达方面存在差异（MCF10A是上皮细胞；MCF12A类似间充质细胞）。HSF1下调导致MCF10A细胞在基质胶中的增殖率降低和球体形成减少。然而，它不影响MCF12A的增殖，但导致CDH1上调和形成组织更良好的球体。MCF10A中HSF1过表达导致CDH1减少和VIM表达增加，并获得伸长的成纤维细胞样形态。上述结果表明，HSF1水平升高可能使乳腺上皮细胞向间充质表型转变，而HSF1水平降低可能使间充质表型逆转为上皮表型。因此HSF1可能参与女性一生中乳腺结构的重塑。此外，HSF1水平与三阴性乳腺癌细胞的侵袭性表型呈正相关，其生长受到HSF1抑制剂DTHIB的抑制。
