LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker.
LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker.
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作者：
迫切需要确定转移性疾病的预后标志物和治疗靶点。结合高通量RNA测序、功能表征、机制研究和临床验证，我们将白血病抑制因子受体（LIFR）鉴定为microRNA miR-9下游和Hippo信号传导上游的乳腺癌转移抑制因子。在高度恶性肿瘤细胞中恢复LIFR表达通过触发Hippo激酶级联反应抑制转移，所述Hippo激酶级联反应导致转录共激活因子YES相关蛋白（雅普）的磷酸化、细胞质滞留和功能失活。相反，非转移性乳腺癌细胞中LIFR的丧失通过雅普的活化诱导迁移、侵袭和转移性定殖。LIFR在人乳腺癌中下调，并与转移呈负相关。值得注意的是，在大约1,000例非转移性乳腺肿瘤中，LIFR表达状态与患者的无转移、无复发和总生存结局相关。这些发现将LIFR鉴定为通过Hippo-YAP途径起作用的转移抑制剂，并且具有显著的预后能力。
There is a pressing need to identify prognostic markers of metastatic disease and targets for treatment. Combining high-throughput RNA sequencing, functional characterization, mechanistic studies and clinical validation, we identify leukemia inhibitory factor receptor (LIFR) as a breast cancer metastasis suppressor downstream of the microRNA miR-9 and upstream of Hippo signaling. Restoring LIFR expression in highly malignant tumor cells suppresses metastasis by triggering a Hippo kinase cascade that leads to phosphorylation, cytoplasmic retention and functional inactivation of the transcriptional coactivator YES-associated protein (YAP). Conversely, loss of LIFR in nonmetastatic breast cancer cells induces migration, invasion and metastatic colonization through activation of YAP. LIFR is downregulated in human breast carcinomas and inversely correlates with metastasis. Notably, in approximately 1,000 nonmetastatic breast tumors, LIFR expression status correlated with metastasis-free, recurrence-free and overall survival outcomes in the patients. These findings identify LIFR as a metastasis suppressor that functions through the Hippo-YAP pathway and has significant prognostic power.
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影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
DOI：
10.1038/nrc2594
发表时间：
2009-04
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.3
作者：
Richardson, AL;Wang, ZGC;Ganesan, S
通讯作者：
Ganesan, S
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
21.3
作者：
Ma, Li;Young, Jennifer;Prabhala, Harsha;Pan, Elizabeth;Mestdagh, Pieter;Muth, Daniel;Teruya-Feldstein, Julie;Reinhardt, Ferenc;Onder, Tamer T.;Valastyan, Scott;Westermann, Frank;Speleman, Frank;Vandesompele, Jo;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.