Related Experiment Video

Updated: Aug 11, 2026

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

RhoC promotes human melanoma invasion in a PI3K/Akt-dependent pathway

Mariah C Ruth1, Yisheng Xu, Ian H Maxwell

  • 1Department of Dermatology, University of Colorado Health Science Center at Fitzsimons, Aurora, Colorado 80045, USA.

The Journal of Investigative Dermatology
|February 14, 2006
PubMed

Insights

RhoC overexpression enhances melanoma cell invasion by activating the PI3K/Akt pathway, independent of Rho-kinase signaling. This suggests RhoC promotes cancer progression through distinct molecular mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • RhoC GTPase overexpression correlates with high metastatic potential and poor prognosis in human cancers.
  • The PI3K/Akt pathway is crucial for neoplastic phenotypes, including cell cycle progression, anti-apoptosis, and invasion.
  • Rho signaling can modulate PI3K/Akt activity, but the precise mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of RhoC in melanoma cell invasion.
  • To elucidate the relationship between RhoC, PI3K/Akt pathway, and Rho-kinase (ROCK) signaling in melanoma progression.

Main Methods:

  • Established stable human melanoma cell lines overexpressing RhoC (WM35RhoC).
  • Utilized C3 transferase to inhibit RhoC activity.
  • Employed inhibitors for PI3K, Akt, and ROCK pathways.
  • Assessed cell invasion and levels of phosphorylated Akt (pAkt).

Main Results:

  • RhoC overexpression increased pAkt levels and melanoma cell invasion.
  • RhoC inhibition reduced pAkt and invasion.
  • Inhibition of PI3K, Akt, or ROCK partially reduced invasion.
  • PI3K inhibition, but not ROCK inhibition, decreased pAkt levels.

Conclusions:

  • RhoC promotes melanoma cell invasion partially through PI3K/Akt pathway activation, independently of ROCK signaling.
  • RhoC may drive melanoma progression via separate pathways regulating PI3K/Akt and ROCK signaling.

More Related Videos

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression11:02

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression

Published on: August 3, 2011

A 3D Organotypic Melanoma Spheroid Skin Model08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

Related Concept Videos

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 rapamycin-insensitive companion...
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...
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:
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...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...