Reference SummaryLiu W, Cancer Cell 2012 Jun 12;21(6):751-64

Title

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

Authors

Liu W; Monahan KB; Pfefferle AD; Shimamura T; Sorrentino J; Chan KT; Roadcap DW; Ollila DW; Thomas NE; Castrillon DH; Miller CR; Perou CM; Wong KK; Bear JE; Sharpless NE

Journal

Cancer Cell

Volume

21

Issue

6

Year

2012

Pages

751-64

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.

Links

J:189285 – Mouse Genome Informatics
22698401 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

0

[not specified]-Stk11tm1.1Rdp Tg(Tyr-cre/ERT2)13Bos Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

0

[not specified]-Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

0

[not specified]-Stk11tm1.1Rdp Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

0

[not specified]-Krastm4Tyj/+ Stk11tm1.1Rdp Tg(Tyr-cre/ERT2)13Bos Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

100

[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

73

[not specified]-Krastm4Tyj/+ Stk11tm1.1Rdp Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

100