Related Experiment Video

Updated: Jun 5, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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

Published on: July 17, 2019

A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition independent of BRAF mutation status

Marie C Zipser1, Ossia M Eichhoff, Daniel S Widmer

  • 1Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

Pigment Cell & Melanoma Research
|December 24, 2010
PubMed

Insights

Melanoma cell phenotype impacts MAPK pathway inhibitor response. Proliferative cells respond initially, but can gain invasive traits, necessitating dual-targeting strategies for effective melanoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • The Mitogen-activated protein kinase (MAPK) pathway is frequently mutated in melanoma.
  • Targeting MAPK signaling provides significant clinical responses in melanoma patients, but resistance often develops.

Purpose of the Study:

  • To investigate the differential response of proliferative and invasive melanoma cell phenotypes to MAPK signaling inhibitors.
  • To determine the influence of BRAF mutation status on treatment response in different melanoma cell phenotypes.

Main Methods:

  • Utilized two distinct MAPK signaling inhibitors.
  • Examined effects on melanoma cell cultures exhibiting proliferative and invasive phenotypes.
  • Assessed responses in cells with various MAPK pathway mutations, including BRAF.

Main Results:

  • Proliferative melanoma cells showed higher susceptibility to MAPK inhibition than invasive cells, regardless of BRAF status.
  • The response of invasive melanoma cells to MAPK inhibition was dependent on BRAF mutation status.
  • Inhibition of MAPK signaling in proliferative cells induced the acquisition of invasive phenotype characteristics.

Conclusions:

  • Melanoma cell phenotype is a critical determinant of response to MAPK pathway inhibitors.
  • Current therapies targeting proliferative melanoma cells may not be sufficient due to the emergence of invasive phenotypes.
  • Future melanoma treatment strategies should consider targeting both proliferative and invasive cell populations.

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

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

Published on: June 7, 2019

A 3D Organotypic Melanoma Spheroid Skin Model08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

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...
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...
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...
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 superfamily...
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...
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...