Related Experiment Video

Updated: May 18, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

RhoJ regulates melanoma chemoresistance by suppressing pathways that sense DNA damage

Hsiang Ho1, Jayavani Aruri, Rubina Kapadia

  • 1Department of Dermatology, University of California at Irvine, Irvine, California 92697, USA.

Cancer Research
|September 14, 2012
PubMed

Insights

Melanoma cells resist chemotherapy by activating RhoJ and PAK1, which blunt the DNA damage response (DDR). Inhibiting RhoJ/PAK1 may overcome this resistance, offering new melanoma treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Melanomas exhibit resistance to conventional chemotherapeutics, often due to impaired apoptotic checkpoint activation.
  • Understanding the molecular mechanisms underlying this resistance is crucial for developing effective treatments.

Purpose of the Study:

  • To identify key regulators of melanoma cell sensitivity to DNA damage using a genome-wide RNA interference screen.
  • To elucidate the role of RhoJ and PAK1 in modulating the DNA damage response (DDR) in melanoma.

Main Methods:

  • Genome-wide RNA interference screening to identify genes affecting melanoma cell sensitivity to DNA damage.
  • Investigating the signaling pathway involving RhoJ, PAK1, and ATR in response to drug-induced DNA damage.
  • Analyzing the phosphorylation status of ATF2 and the expression of Sox10.

Main Results:

  • RhoJ and its effector PAK1 were identified as critical modulators of melanoma cell sensitivity to DNA damage.
  • RhoJ activation of PAK1 uncouples ATR from downstream effectors, leading to a blunted DNA damage response (DDR).
  • ATR suppression decreases ATF2 phosphorylation and increases Sox10 expression, raising the threshold for melanoma cell death.

Conclusions:

  • The RhoJ/PAK1 pathway plays a significant role in chemoresistance in melanoma by dampening the DNA damage response.
  • Targeting RhoJ/PAK1 in combination with DNA damaging agents presents a promising therapeutic strategy for resistant melanomas.

More Related Videos

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes08:32

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

Published on: May 23, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

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...
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...
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.
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 daughter...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...