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

AUTOR(ES)

Henriet, Patrick

FONTE

The National Academy of Sciences

RESUMO

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 G1/S checkpoint and maintain high levels of p27KIP1 mRNA and protein. In contrast, on nonfibrillar (denatured) collagen, the cells enter the cell cycle, and p27KIP1 is down-regulated. These growth regulatory effects involve contact between type I collagen and the collagen-binding integrin α2β1, 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.

Documentos Relacionados

• Stat Proteins Control Lymphocyte Proliferation by Regulating p27Kip1 Expression
• Gibberellins Promote Trichome Formation by Up-Regulating GLABROUS1 in Arabidopsis1
• Transforming Growth Factor-β1 (TGF-β1) Induces Human Osteoclast Apoptosis by Up-regulating Bim*
• Gene disruption of p27Kip1 allows cell proliferation in the postnatal and adult organ of Corti
• Expression of constitutively active 4EBP-1 enhances p27Kip1 expression and inhibits proliferation of MCF7 breast cancer cells