AR-mTOR-SRF Axis Regulates HMMR Expression in Human Prostate Cancer Cells.

Biomolecules & Therapeutics
You SunKyung Song

Abstract

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment...Continue Reading

References

Nov 22, 2001·The Journal of Biological Chemistry·Eva A TurleyLilly Y W Bourguignon
Jun 17, 2003·Molecular Biology of the Cell·Christopher A MaxwellLinda M Pilarski
Feb 3, 2004·Journal of Cellular Biochemistry·Mary-Ellen Taplin, Steven P Balk
Apr 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mujib RahmanChawnshang Chang
Jul 26, 2006·Carcinogenesis·Shi-Lung LinShao-Yao Ying
Nov 4, 2006·Cell·Vladimir JoukovDavid M Livingston
Oct 9, 2007·Nature Genetics·Miguel Angel PujanaMarc Vidal
Jan 5, 2008·Carcinogenesis·Shi-Lung LinShao-Yao Ying
Mar 21, 2008·Journal of Cell Science·Christopher Alan MaxwellEva Turley
Jun 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Inti ZlobecAlessandro Lugli
Sep 3, 2009·Neoplasia : an International Journal for Oncology Research·Kilian M GustMark Ringhoffer
Oct 20, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Hiroko HatanoNobuyuki Kamata
Jul 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kai-Hsiung ChangNima Sharifi
Oct 15, 2011·International Journal of Clinical Practice·M KirbyE D Crawford
Dec 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Zhongyuan WangLaiqiang Huang
Nov 14, 2015·Nature Reviews. Cancer·Philip A WatsonCharles L Sawyers
Oct 5, 2016·Oncology Letters·Ke Wang, Tao Zhang
Dec 8, 2016·Cancer Research·Chellappagounder ThangavelRobert B Den
Mar 12, 2017·Cell·Robert A Saxton, David M Sabatini
Apr 8, 2017·Cell·Robert A Saxton, David M Sabatini
Oct 27, 2018·Molecular Carcinogenesis·Jung Min SongFekadu Kassie
Jul 23, 2020·Biochemistry and Biophysics Reports·Jing ZhangZhiping Wang
Aug 8, 2020·Genes·Lucas TafurRobbie Loewith
Sep 10, 2020·Genes·Wenxiang Fu, Michael N Hall
Sep 24, 2020·European Journal of Medicinal Chemistry·Yifan Chen, Xiaoping Zhou

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.