Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling Journal Article
| Authors: | Gao, H.; Chakraborty, G.; Zhang, Z.; Akalay, I.; Gadiya, M.; Gao, Y.; Sinha, S.; Hu, J.; Jiang, C.; Akram, M.; Brogi, E.; Leitinger, B.; Giancotti, F. |
| Article Title: | Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling |
| Abstract: | 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 PKCα. 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. © 2016 Elsevier Inc. |
| Journal Title: | Cell |
| Volume: | 166 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2016-06-30 |
| Start Page: | 47 |
| End Page: | 62 |
| Language: | English |
| DOI: | 10.1016/j.cell.2016.06.009 |
| PROVIDER: | scopus |
| PUBMED: | 27368100 |
| PMCID: | PMC4980842 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2016 -- Source: Scopus |
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