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.

journal_name

Cell

journal_title

Cell

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 FG

doi

10.1016/j.cell.2016.06.009

subject

Has Abstract

pub_date

2016-06-30 00:00:00

pages

47-62

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(16)30738-3

journal_volume

166

pub_type

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