HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1.

Abstract
It is known that the extracellular matrix regulates normal cell proliferation, and it is assumed that anchorage-independent malignant cells escape this regulatory function. Here we demonstrate that human M24met melanoma cells remain responsive to growth regulatory signals that result from contact with type I collagen and that the effect on proliferation depends on the physical structure of the collagen. On polymerized fibrillar collagen, M24met cells are growth arrested at the G(1)/S checkpoint and maintain high levels of p27(KIP1) mRNA and protein. In contrast, on nonfibrillar (denatured) collagen, the cells enter the cell cycle, and p27(KIP1) is down-regulated. These growth regulatory effects involve contact between type I collagen and the collagen-binding integrin alpha(2)beta(1), which appears restricted in the presence of fibrillar collagen. Thus melanoma cells remain sensitive to negative growth regulatory signals originating from fibrillar collagen, and the proteolytic degradation of fibrils is a mechanism allowing tumor cells to escape these restrictive signals.
AuthorsP Henriet, Z D Zhong, P C Brooks, K I Weinberg, Y A DeClerck
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 97 Issue 18 Pg. 10026-31 (Aug 29 2000) ISSN: 0027-8424 [Print] United States
PMID10944199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cell Cycle Proteins
  • Extracellular Matrix Proteins
  • Integrins
  • Microtubule-Associated Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Collagen
  • Cyclin-Dependent Kinases
Topics
  • Apoptosis
  • Cell Cycle (physiology)
  • Cell Cycle Proteins
  • Cell Division (drug effects, physiology)
  • Collagen (pharmacology, physiology)
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases (antagonists & inhibitors)
  • Extracellular Matrix Proteins (physiology)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrins (genetics, physiology)
  • Kinetics
  • Melanoma
  • Microtubule-Associated Proteins (genetics)
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: