文献详情
Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling
文献类型期刊论文
通讯作者Gao, H (reprint author), Tongji Univ, Shanghai East Hosp, Res Ctr Translat Med,Metastasis Res Inst, Key Lab Arrhythmias,Minist Educ China,Breast Canc, Shanghai 200092, Peoples R China.; Gao, H (reprint author), Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Shanghai 200092, Peoples R China.; Gao, H; Giancotti, FG (reprint author), Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA.; Gao, H; Giancotti, FG (reprint author), Mem Sloan Kettering Canc Ctr, Ctr Met
2016
期刊名称CELL影响因子和分区
166
1
页码范围47-62
增刊正刊
收录情况SCI(E)(WOS:000380254400010)  PubMed(27368100)  
所属部门生命科学与技术学院
语言外文
ISSN0092-8674
DOI10.1016/j.cell.2016.06.009
被引频次11
人气指数3283
浏览次数3271
基金NIH [R01 CA175712, R35 CA197566, P01 CA094060]; Geoffrey Beene Cancer Center of MSKCC; National Basic Research program of China (973 Program) [2015CB964800]; National Natural Science Foundation of China [81372840]; One Thousand Talents Program of Shanghai [SH04020]; Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81221001]; Program for Professors of Special Appointment at Shanghai Institutions of Higher Learning; China Scholarship Council
摘要Genetic screening identifies the atypical tetraspanin TM4SF1 as a strong mediator of metastatic reactivation of breast cancer. Intriguingly, TM4SF1 couples the collagen receptor tyrosine kinase DDR1 to the cortical adaptor syntenin 2 and, hence, to PKC alpha. The latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3. This non-canonical mechanism of signaling induces the expression of SOX2 and NANOG; sustains the manifestation of cancer stem cell traits; and drives metastatic reactivation in the lung, bone, and brain. Bioinformatic analyses and pathological studies corroborate the clinical relevance of these findings. We conclude that non-canonical DDR1 signaling enables breast cancer cells to exploit the ubiquitous interstitial matrix component collagen I to undergo metastatic reactivation in multiple target organs.
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