文摘
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Summary
Germline mutations in m>LKB1m> (m>STK11m>) are associated with the Peutz-Jeghers syndrome (PJS), which includes aberrant mucocutaneous pigmentation, and somatic m>LKB1m> mutations occur in 10 % of cutaneous melanoma. By somatically inactivating m>Lkb1m> with m>K-Rasm> activation (¡Àm>p53m> loss) in murine melanocytes, we observed variably pigmented and highly metastatic melanoma with 100 % penetrance. LKB1 deficiency resulted in increased phosphorylation of the SRC family kinase (SFK) YES, increased expression of WNT target genes,?and expansion of a CD24+ cell population, which showed increased metastatic behavior in?vitro and in?vivo relative to isogenic CD24?/sup> cells. These results suggest that m>LKB1m> inactivation in the context of RAS activation facilitates metastasis by inducing an SFK-dependent expansion of a prometastatic, CD24+ tumor subpopulation.