Related Experiment Video

Updated: Aug 26, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

8.9K

RSK2 promotes melanoma cell proliferation and vemurafenib resistance via upregulating cyclin D1

Hai-Zhou Wu1,2, Lan-Ya Li1,2, Shi-Long Jiang1

  • 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.

Frontiers in Pharmacology
|October 10, 2022
PubMed

Insights

Overexpression of RSK2 in melanoma drives resistance to BRAF inhibitors like vemurafenib. Targeting RSK2 may overcome this resistance, improving patient survival in BRAF-mutant melanoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • BRAF inhibitors are crucial for treating BRAFV600E mutant melanoma.
  • Acquired resistance to BRAF inhibitors limits treatment efficacy.
  • Identifying resistance mechanisms is vital for improving melanoma therapy.

Purpose of the Study:

  • To investigate the role of RSK2 in BRAF inhibitor resistance in melanoma.
  • To elucidate the molecular mechanism by which RSK2 contributes to resistance.
  • To explore RSK2 as a potential therapeutic target.

Main Methods:

  • Analysis of RSK2 expression in melanoma patient data.
  • Experimental manipulation of RSK2 levels (overexpression and deletion) in melanoma cells.
  • Assessment of cell proliferation and sensitivity to vemurafenib.
  • Investigation of protein-protein interactions and phosphorylation events (RSK2, FOXO1, cyclin D1).

Main Results:

  • RSK2 is overexpressed in melanoma and correlates with poor patient survival.
  • RSK2 overexpression confers resistance to vemurafenib, while RSK2 deletion sensitizes cells to the drug.
  • RSK2 interacts with FOXO1, promoting its phosphorylation and degradation.
  • RSK2-mediated degradation of FOXO1 leads to cyclin D1 upregulation.

Conclusions:

  • A novel RSK2-FOXO1-cyclin D1 signaling pathway is identified in melanoma.
  • RSK2 plays a critical role in mediating vemurafenib resistance.
  • Targeting RSK2 presents a potential strategy to enhance vemurafenib efficacy in melanoma treatment.
Keywords:
FoxO1Rsk2cyclin D1melanomavemurafenib

More Related Videos

Author Spotlight: Assessing the Potential of Circulating Tumor Cells in Leptomeningeal Disease Research06:25

Author Spotlight: Assessing the Potential of Circulating Tumor Cells in Leptomeningeal Disease Research

Published on: March 29, 2024

987
A 3D Organotypic Melanoma Spheroid Skin Model08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

15.9K

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
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...
4.9K
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...
5.9K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
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
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K