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

Authors: Liu, Wenjin; Monahan, Kimberly B; Pfefferle, Adam D; Shimamura, Takeshi; Sorrentino, Jessica; Chan, Keefe T; Roadcap, David W; Ollila, David W; Thomas, Nancy E; Castrillon, Diego H; Miller, C Ryan; Perou, Charles M; Wong, Kwok-Kin; Bear, James E; Sharpless, Norman E

Published In Cancer Cell, (2012 Jun 12)

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.

PubMed ID: 22698401

MeSH Terms: No MeSH terms associated with this publication