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-a...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/151472 |
| _version_ | 1826112196975788032 |
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| author | Tan, Sijie Bajalovic, Natasa Wong, Esther S. P. Lin, Valerie Chun Ling |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Tan, Sijie Bajalovic, Natasa Wong, Esther S. P. Lin, Valerie Chun Ling |
| author_sort | Tan, Sijie |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:03:01Z |
| format | Journal Article |
| id | ntu-10356/151472 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:03:01Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1514722021-06-16T07:41:42Z Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells Tan, Sijie Bajalovic, Natasa Wong, Esther S. P. Lin, Valerie Chun Ling School of Biological Sciences Yong Loo Lin School of Medicine, National University of Singapore Science::Biological sciences Autophagy Breast Cancer 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. Ministry of Education (MOE) This work is supported by Singapore Ministry of Education Academic Research Fund Tier 2, MOE2014-T2-2-125. 2021-06-16T07:41:42Z 2021-06-16T07:41:42Z 2019 Journal Article Tan, S., Bajalovic, N., Wong, E. S. P. & Lin, V. C. L. (2019). Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells. Experimental Cell Research, 382(1), 111433-. https://dx.doi.org/10.1016/j.yexcr.2019.05.014 0014-4827 https://hdl.handle.net/10356/151472 10.1016/j.yexcr.2019.05.014 31100306 2-s2.0-85066095580 1 382 111433 en MOE2014-T2-2-125 Experimental Cell Research © 2019 Elsevier Inc. All rights reserved. |
| spellingShingle | Science::Biological sciences Autophagy Breast Cancer Tan, Sijie Bajalovic, Natasa Wong, Esther S. P. Lin, Valerie Chun Ling Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells |
| title | Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells |
| title_full | Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells |
| title_fullStr | Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells |
| title_full_unstemmed | Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells |
| title_short | Ligand-activated progesterone receptor B activates transcription factor EB to promote autophagy in human breast cancer cells |
| title_sort | ligand activated progesterone receptor b activates transcription factor eb to promote autophagy in human breast cancer cells |
| topic | Science::Biological sciences Autophagy Breast Cancer |
| url | https://hdl.handle.net/10356/151472 |
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