Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells MCF-7.

Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells MCF-7. Exp Cell Res. 2019 May 14;: Authors: Tan S, Natasa B, Wong ESP, Lin VCL Abstract Autophagy is an evolutionary conserved, self-eating process that targets cellular constituents for lysosomal degradation. Transcription factor EB (TFEB) is a master regulator of autophagy by inducing the expression of genes involved in autophagic and lysosomal degradation. In breast cancer, ligand-activated progesterone receptor has been reported to influence cancer development by manipulating the autophagy pathway. However, understanding of the mechanism that underlies the autophagic response remains limited. Herein, we report that prolonged treatment with progestin R5020 upregulates autophagy in MCF-7 human breast cancer cells via a novel interplay between progesterone receptor B (PRB) and TFEB. R5020 upregulates TFEB gene expression and protein levels in a PRB-dependent manner. Additionally, R5020 enhances the co-recruitment of PRB and TFEB to each other to facilitate TFEB nuclear localization. Once in the nucleus, TFEB induces expression of autophagy and lysosomal genes to potentiate autophagy in MCF-7 cells. Together, our findings highlight a novel functional connection between ligand-activated PRB and TFEB to modulate autophagy in MCF-7 breast cancer cells. As breast cancer development is controlled by autophagy, the...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research