These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Adhesion-dependent activation of the ERK1/2 cascade is by-passed in melanoma cells.
    Author: Conner SR, Scott G, Aplin AE.
    Journal: J Biol Chem; 2003 Sep 05; 278(36):34548-54. PubMed ID: 12821662.
    Abstract:
    Normal cells are dependent upon integrin-mediated adhesion to the extracellular matrix for cell proliferation and survival. Integrins regulate these processes partially through control of extracellular signal-regulated kinases 1 and 2 (ERK1/2). A trait of malignant cells is their ability to undergo anchorage-independent growth. Melanomas are tumors arising from normal melanocytes that, if undetected at an early stage, are highly invasive and poorly treatable. Proliferation of melanoma cells and melanocytes is dependent upon ERK1/2 signaling, and mutation of B-Raf, a component of the ERK1/2 pathway, is commonly found in melanomas. We addressed the role of integrin-mediated adhesion in ERK1/2 signaling in human melanoma cells and primary melanocytes. Basal ERK1/2 activity was low, and growth factor activation was adhesion-dependent in normal human melanocytes. By contrast in mutant B-Raf-expressing melanoma cells (SK-MEL-24 and SK-MEL-28), the ERK1/2 pathway was constitutively active, and adhesion-dependent regulation of ERK1/2 activity was by-passed. Furthermore, in melanoma cells, ERK1/2 translocated to the nucleus and regulated transcription events in an adhesion-independent manner. Expression of mutant V599E B-Raf in normal melanocytes was sufficient to promote adhesion-independent ERK1/2 signaling. These results indicate that alterations in the adhesion requirement for ERK1/2 signaling in melanocytes are associated with the acquisition of malignant cell behavior.
    [Abstract] [Full Text] [Related] [New Search]