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Cancer Cell. 2012 Jun 12;21(6):751-64. doi: 10.1016/j.ccr.2012.03.048.

LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma.

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1
Department of Genetics, The Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7295, USA.

Abstract

Germline mutations in LKB1 (STK11) are associated with the Peutz-Jeghers syndrome (PJS), which includes aberrant mucocutaneous pigmentation, and somatic LKB1 mutations occur in 10% of cutaneous melanoma. By somatically inactivating Lkb1 with K-Ras activation (±p53 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(-) cells. These results suggest that LKB1 inactivation in the context of RAS activation facilitates metastasis by inducing an SFK-dependent expansion of a prometastatic, CD24(+) tumor subpopulation.

PMID:
22698401
PMCID:
PMC3660964
DOI:
10.1016/j.ccr.2012.03.048
[Indexed for MEDLINE]
Free PMC Article

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