Related Experiment Video

Updated: Jan 3, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.3K

MYSM1-AR complex-mediated repression of Akt/c-Raf/GSK-3β signaling impedes castration-resistant prostate cancer

Jinbo Sun1, Xiangnan Hu1, Yongheng Gao2

  • 1Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.

Aging
|November 26, 2019
PubMed

Insights

Histone deubiquitinase MYSM1 is downregulated in castration-resistant prostate cancer (CRPC). MYSM1 loss promotes CRPC cell proliferation and tumor growth, suggesting MYSM1 as a potential therapeutic target for prostate cancer.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Castration-resistant prostate cancer (CRPC) progression involves epigenetic alterations impacting gene expression.
  • The role of histone deubiquitinase MYSM1 in prostate cancer (PCa) pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the role of MYSM1 in prostate cancer progression, particularly in CRPC.
  • To determine the functional impact of MYSM1 on cancer cell behavior and tumorigenesis.

Main Methods:

  • Analysis of MYSM1 expression in PCa tissues and public datasets.
  • In vitro and in vivo studies assessing the effects of MYSM1 knockdown on cell proliferation, senescence, and viability.
  • Integrative bioinformatic analyses and co-immunoprecipitation assays to identify MYSM1-associated pathways and interactions.

Main Results:

  • MYSM1 expression was found to be downregulated in CRPC compared to localized prostate tumors.
  • MYSM1 knockdown accelerated CRPC cell proliferation, inhibited senescence under androgen-depleted conditions, and enhanced tumor growth in vivo.
  • MYSM1 interacts with the androgen receptor and influences the Akt/c-Raf/GSK-3β signaling pathway.

Conclusions:

  • MYSM1 plays a critical role in the pathogenesis of CRPC.
  • MYSM1 downregulation contributes to CRPC progression by promoting proliferation and enhancing tumorigenicity.
  • MYSM1 represents a potential therapeutic target for treating prostate cancer.
Keywords:
ARAktMYSM1castration-resistant prostate cancergrowth

More Related Videos

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.7K
Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

7.0K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.7K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
11.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K