期刊
CELL
卷 166, 期 1, 页码 47-62出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.06.009
关键词
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资金
- 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
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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