LKB1/STK11 Inactivation Leads to Expansion of a Prometastatic Tumor Subpopulation in Melanoma

详细信息	查看全文 | 推荐本文 |

• 作者：Wenjin Liu<sup>1sup> ; Kimberly  ; B. Monahan<sup>1sup> ; Adam  ; D. Pfefferle<sup>2sup> ; Takeshi Shimamura<sup>9sup> ; Jessica Sorrentino<sup>1sup> ; Keefe  ; T. Chan<sup>3sup><sup> ; sup><sup>4sup> ; David  ; W. Roadcap<sup>3sup> ; David  ; W. Ollila<sup>7sup> ; Nancy  ; E. Thomas<sup>6sup> ; Diego  ; H. Castrillon<sup>10sup> ; C.  ; Ryan Miller<sup>2sup> ; Charles  ; M. Perou<sup>1sup><sup> ; sup><sup>2sup><sup> ; sup><sup>8sup> ; Kwok-Kin Wong<sup>11sup> ; James  ; E. Bear<sup>3sup><sup> ; sup><sup>4sup> ; Norman  ; E. Sharpless<sup>1sup><sup> ; sup><sup>5sup><sup> ; sup><sup>nes@med.unc.edusup>
• 刊名：Cancer Cell
• 出版年：2012
• 期刊代码：43_15356108
• 类别：med
• 出版时间：12 June, 2012
• 卷：21
• 期：6
• 页码：751-764
• 文件大小：1981 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferencesml version="1.0" encoding="UTF-8"?>

ss="h3">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 (卤m>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,聽and expansion of a CD24<sup>+sup> cell population, which showed increased metastatic behavior in聽vitro and in聽vivo relative to isogenic CD24<sup>鈭?/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<sup>+sup> tumor subpopulation.