Related Experiment Video

Updated: Aug 24, 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

SRC-RAC1 signaling drives drug resistance to BRAF inhibition in de-differentiated cutaneous melanomas

Eliot Y Zhu1,2,3,4, Jesse D Riordan1,2, Marion Vanneste2,5

  • 1Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA, USA.

NPJ Precision Oncology
|October 21, 2022
PubMed

Insights

Wildtype RAC1 and SRC drive drug resistance in de-differentiated cutaneous melanoma. A ten-gene panel simplifies classifying melanoma differentiation status for targeted therapy.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Targeted BRAF inhibition is a key treatment for cutaneous melanoma.
  • Drug resistance, often driven by mutations like RAC1, limits BRAF inhibitor efficacy.
  • Melanoma subtypes exhibit distinct biological behaviors and treatment responses.

Purpose of the Study:

  • To investigate the role of wildtype RAC1 and SRC in BRAF inhibitor resistance in cutaneous melanoma.
  • To identify biomarkers for predicting response to targeted therapies.
  • To develop a simplified method for classifying melanoma differentiation status.

Main Methods:

  • Analysis of wildtype RAC1 and SRC activity in melanoma cell lines.
  • Assessment of drug sensitivity to BRAF inhibitors in relation to differentiation markers.
  • Development and validation of a ten-gene classifier for melanoma differentiation status.

Main Results:

  • Wildtype RAC1 drives growth and drug resistance in de-differentiated melanomas.
  • SRC inhibition selectively sensitizes de-differentiated melanomas to BRAF inhibition.
  • A ten-gene panel accurately classifies melanoma differentiation status, simplifying previous hundreds-of-genes methods.

Conclusions:

  • De-differentiation status is a critical factor in BRAF inhibitor response in cutaneous melanoma.
  • Targeting RAC1 and SRC presents potential therapeutic strategies for de-differentiated melanomas.
  • A practical gene-based classification system can enhance precision medicine for melanoma treatment.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.1K
Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

3.0K

Related Concept Videos

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
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...
6.4K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.1K
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
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K
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...
4.6K