mTORC1 Activation Blocks BrafV600E-Induced Growth Arrest but Is Insufficient for Melanoma Formation
作者： William Damsky , Goran Micevic , Katrina Meeth , Viswanathan Muthusamy , David P. Curley
DOI: 10.1016/J.CCELL.2014.11.014
关键词:
摘要: Braf(V600E) induces benign, growth-arrested melanocytic nevus development, but also drives melanoma formation. Cdkn2a loss in melanocytes mice results rare progression to melanoma, only after stable growth arrest as nevi. Immediate is prevented by upregulation of miR-99/100, which downregulates mTOR and IGF1R signaling. mTORC1 activation through Stk11 (Lkb1) abrogates nevi, insufficient for complete melanoma. associated with mTORC2 Akt human murine neoplasms. Simultaneous Lkb1 inactivation both mTORC2/Akt, inducing rapid formation mice. In this model, mTORC1/2 required Braf-induced melanomagenesis.
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