Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis - PubMed (original) (raw)

Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis

Randolph S Watnick et al. Cancer Cell. 2003 Mar.

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Retraction in

• Retraction. Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis.
  [No authors listed] [No authors listed] Cancer Cell. 2013 Jan 14;23(1):129. doi: 10.1016/j.ccr.2012.11.004. Cancer Cell. 2013. PMID: 23447819 No abstract available.

Abstract

Tumor angiogenesis is postulated to be regulated by the balance between pro- and anti-angiogenic factors. We demonstrate that the critical step in establishing the angiogenic capability of human cells is the repression of the critical anti-angiogenic factor, thrombospondin-1 (Tsp-1). This repression is essential for tumor formation by mammary epithelial cells and kidney cells engineered to express SV40 early region proteins, hTERT, and H-RasV12. We have uncovered the signaling pathway leading from Ras to Tsp-1 repression. Ras induces the sequential activation of PI3 kinase, Rho, and ROCK, leading to activation of Myc through phosphorylation; phosphorylation of Myc via this mechanism enables it to repress Tsp-1 expression. We thus describe a novel mechanism by which the cooperative activity of the oncogenes, ras and myc, leads directly to angiogenesis and tumor formation.

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Comment in

• Wiring the angiogenic switch: Ras, Myc, and Thrombospondin-1.
  Volpert OV, Alani RM. Volpert OV, et al. Cancer Cell. 2003 Mar;3(3):199-200. doi: 10.1016/s1535-6108(03)00056-4. Cancer Cell. 2003. PMID: 12676576

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