E-GEOD-34866 - LKB1/STK11 Inactivation Leads to Expansion of Pro-Metastatic Tumor Sub-Population in Melanoma

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

LKB1/STK11 Inactivation Leads to Expansion of Pro-Metastatic Tumor Sub-Population in Melanoma

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 and the subsequent 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 a SFK-dependent expansion of a pro-metastatic, CD24+ tumor sub-population reference x sample

ORGANISM(S): Mus musculus

SUBMITTER: Charles Perou

PROVIDER: E-GEOD-34866 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Liu Wenjin W Monahan Kimberly B KB Pfefferle Adam D AD Shimamura Takeshi T Sorrentino Jessica J Chan Keefe T KT Roadcap David W DW Ollila David W DW Thomas Nancy E NE Castrillon Diego H DH Miller C Ryan CR Perou Charles M CM Wong Kwok-Kin KK Bear James E JE Sharpless Norman E NE

Cancer cell 20120601 6

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 targ ...[more]

PMID: 22698401

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