Related Experiment Video

Updated: Sep 19, 2025

Murine Prostate Micro-dissection and Surgical Castration
08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

46.1K

RSK1-driven TRIM28/E2F1 feedback loop promotes castration-resistant prostate cancer progression

Miyeong Kim1, Jinpeng Liu2, Yanquan Zhang1

  • 1Department of Toxicology and Cancer Biology.

The Journal of Clinical Investigation
|June 16, 2025
PubMed

Insights

Castration-resistant prostate cancer (CRPC) progression is driven by the RSK1-TRIM28-E2F1 axis. Targeting this pathway, particularly TRIM28 phosphorylation, offers a potential vulnerability for treating advanced prostate cancer.

Area of Science:

  • Molecular oncology
  • Cancer biology

Background:

  • Castration-resistant prostate cancer (CRPC) is an advanced, lethal stage of prostate cancer (PCa).
  • TRIM28 (KAP1) promotes CRPC cell proliferation and tumor growth, but its regulatory mechanisms and targets in CRPC remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms of TRIM28 upregulation in CRPC.
  • To identify genomic targets regulated by TRIM28.
  • To investigate the role of the RSK1-TRIM28-E2F1 axis in CRPC progression.

Main Methods:

  • Integrated genomic analysis to identify TRIM28 as an E2F1 target.
  • Investigated TRIM28/E2F1 feedback loop independent of retinoblastoma (Rb) status.
  • Identified RSK1 as the kinase phosphorylating TRIM28 at S473.

Main Results:

  • TRIM28 is a direct E2F1 target in CRPC, forming a positive feedback loop.
  • RSK1 directly phosphorylates TRIM28 (pS473-TRIM28), driving the TRIM28/E2F1 loop.
  • pS473-TRIM28 promotes CRPC progression; RSK inhibition mitigates this effect.

Conclusions:

  • The RSK1-TRIM28-E2F1 axis is critical for CRPC progression.
  • This axis represents a potential therapeutic vulnerability, especially in Rb-deficient CRPC.
Keywords:
Cell biologyEndocrinologyProstate cancer

More Related Videos

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

6.9K
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

13.3K

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...
3.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
36.2K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.8K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.5K
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...
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...
4.0K