Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells.
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 this 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 the expression of autophagy and lysosomal genes to potentiate autophagy. 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 progestin-PRB-TFEB transduction pathway warrants future attention as a potential therapeutic target in cancer therapy.
['Tan|Sijie|S|', 'Bajalovic|Natasa|N|', 'Wong|Esther S P|ESP|', 'Lin|Valerie C L|VCL|']
D000230:Adenocarcinoma D000071182:Autophagosomes D001343:Autophagy D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors D001943:Breast Neoplasms D045744:Cell Line, Tumor D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008247:Lysosomes D061986:MCF-7 Cells D008869:Microtubule-Associated Proteins D009363:Neoplasm Proteins D011397:Promegestone D025941:Protein Interaction Mapping D021381:Protein Transport D011980:Receptors, Progesterone D011994:Recombinant Proteins D015398:Signal Transduction D015533:Transcriptional Activation
Autophagy Breast cancer TFEB R5020 MCF-7 PRB