LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma.
LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma.
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DOI：
10.1016/j.ccr.2012.03.048
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发表时间：
2012-06-12
期刊：
影响因子：
50.3
通讯作者：
Sharpless NE
中科院分区：
文献类型：
--
作者：
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
LKB 1（STK 11）的种系突变与Peutz-Jeghers综合征（PJS）相关，PJS包括异常的粘膜皮肤色素沉着，10%的皮肤黑色素瘤发生体细胞LKB 1突变。在小鼠黑素细胞中，通过K-Ras激活（±p53丢失）使Lkb 1体细胞失活，我们观察到100%转移率的色素沉着和高转移性黑色素瘤。LKB 1缺陷导致SRC家族激酶（SFK）磷酸化增加，WNT靶基因表达增加，CD 24+细胞群扩增，相对于同基因CD 24 −细胞，体外和体内转移行为增加。这些结果表明，在RAS激活的情况下，LKB 1失活通过诱导促转移性CD 24+肿瘤亚群的SFK依赖性扩增而促进转移。
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.
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影响因子：
50.3
作者：
Carretero J;Shimamura T;Rikova K;Jackson AL;Wilkerson MD;Borgman CL;Buttarazzi MS;Sanofsky BA;McNamara KL;Brandstetter KA;Walton ZE;Gu TL;Silva JC;Crosby K;Shapiro GI;Maira SM;Ji H;Castrillon DH;Kim CF;García-Echeverría C;Bardeesy N;Sharpless NE;Hayes ND;Kim WY;Engelman JA;Wong KK
通讯作者：
Wong KK
影响因子：
6.2
作者：
Kluger, Harriet M.;Dudek, Arkadiuz Z.;McCann, Carrie;Ritacco, Jean;Southard, Nadine;Jilaveanu, Lucia B.;Molinaro, Annette;Sznol, Mario
通讯作者：
Sznol, Mario
影响因子：
64.8
作者：
Ji, Hongbin;Ramsey, Matthew R.;Wong, Kwok-Kin
通讯作者：
Wong, Kwok-Kin
影响因子：
7.3
作者：
Cheng H;Liu P;Wang ZC;Zou L;Santiago S;Garbitt V;Gjoerup OV;Iglehart JD;Miron A;Richardson AL;Hahn WC;Zhao JJ
通讯作者：
Zhao JJ
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA