Involvement of β-catenin in Androgen-induced Mesenchymal Transition of Breast MDA-MB-453 Cancer Cells

Androgen downregulates desmocollin‐2 in association with induction of mesenchymal transition of breast MDA‐MB‐453 cancer cells

“…Several EMT-regulatory genes have simultaneous changes of expression such as β-catenin, Slug, and DSC2. These changes were concurrent with increased cell migration and morphological and cytoskeletal changes, both of which are dependent on β-catenin and Slug (Ahram et al, 2021). The DHT-induced decrease in the expression of DSC2 was not observed in another mesenchymal TNBC cell line, MDA-MB-231 cells indicating that it is cell type-specific (Ahram et al, 2021).…”

“…These changes were concurrent with increased cell migration and morphological and cytoskeletal changes, both of which are dependent on β-catenin and Slug (Ahram et al, 2021). The DHT-induced decrease in the expression of DSC2 was not observed in another mesenchymal TNBC cell line, MDA-MB-231 cells indicating that it is cell type-specific (Ahram et al, 2021). Since the role of DSC2 has not been well studied either in breast cancer or in relation to androgens, this study aimed to unravel the androgen regulation of DSC2 and to elucidate the role of DSC2 in DHT-induced mesenchymal transition of MDA-MB-453 cells.…”

“…Yet, some studies have also shown that AR is also associated with lymph node involvement of TNBC (Astvatsaturyan, Yue, Walts, & Bose, 2018;Shen et al, 2018;Wang et al, 2016). Work on breast cancer cell lines has also shown that treatment of breast cancer cells with androgen induces cell migration and invasion (Ahram et al, 2021;Giovannelli, Di Donato, Auricchio, Castoria, & Migliaccio, 2019;Graham et al, 2009). Using MDA-MB-453 cells as a model system of triple-negative, luminal AR breast cancer, we and others have shown that androgens induce an alteration of cell morphology into a polarized mesenchymal phenotype with a leading edge and a tail and cells appear as single entities rather than clustered groups (Ahram et al, 2018;Giovannelli et al, 2019;Ni et al, 2011).…”

“…We have previously shown that DHT induces the mesenchymal transition of MDA-MB-453 cells resulting in a change in cell morphology from an epithelial, rounded phenotype with cell-cell interactions and cell clustering into an elongated, mesenchymal shape with reduced cell-cell interactions and clustering (Ahram et al, 2017(Ahram et al, , 2018(Ahram et al, , 2021. The morphological change accompanies a significant modification of the actin cytoskeleton; normally in these cells, actin filaments localize in the cortical region of the cells and are organized as arrays directed in different directions toward the basal of the cells, and they become when treated with DHT, structured as paralleled filaments oriented toward the cell tail and organized as a network mesh in the leading edge of the cells.…”

The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

“…In fact, AR activation controls cell cycle progression by increasing cyclin D1 expression while reducing p73 and p21 levels [ 34 ], and promotes epithelial–mesenchymal transition, migration and invasiveness in AR+ TNBC cell lines. Accordingly, blocking AR activity and synthesis reduces tumour growth in patient-derived xenograft models [ 35 , 36 ]. Since a similar pro-tumorigenic role of AR has also been observed in ERα-/HER2-positive (HER2+) breast cancers [ 37 ], AR blockage has been proposed as an effective treatment strategy in ERα- breast cancer [ 38 , 39 , 40 ].…”