PT  - JOURNAL ARTICLE
AU  - Avery Van Duzer
AU  - Sachiko Taniguchi
AU  - Ajit Elhance
AU  - Takahiro Tsujikawa
AU  - Naoki Oshimori
TI  - ADAP1 promotes invasive squamous cell carcinoma progression and predicts patient survival
AID  - 10.26508/lsa.201900582
DP  - 2019 Dec 01
TA  - Life Science Alliance
PG  - e201900582
VI  - 2
IP  - 6
4099  - https://www.life-science-alliance.org/content/2/6/e201900582.short
4100  - https://www.life-science-alliance.org/content/2/6/e201900582.full
SO  - Life Sci. Alliance2019 Dec 01; 2
AB  - Invasive squamous cell carcinoma (SCC) is aggressive cancer with a high risk of recurrence and metastasis, but the critical determinants of its progression remain elusive. Here, we identify ADAP1, a GTPase-activating protein (GAP) for ARF6 up-regulated in TGF-β-responding invasive tumor cells, as a strong predictor of poor survival in early-stage SCC patients. Using a mouse model of SCC, we show that ADAP1 overexpression promotes invasive tumor progression by facilitating cell migration and breakdown of the basement membrane. We found that ADAP1-rich, TGF-β-responding tumor cells exhibit cytoplasmic laminin localization, which correlated with the absence of laminin and type IV collagen from the pericellular basement membrane. Interestingly, although tumors overexpressing a GAP activity-deficient mutant of ADAP1 resulted in morphologically complex tumors, those tumor cells failed to breach the basement membrane. Moreover, Adap1 deletion in tumor cells ameliorated the basement membrane breakdown and had less invading cells in the stroma. Our study demonstrates that ADAP1 is a critical mediator of TGF-β-induced cancer invasion and might be exploited for the treatment of high-risk SCC.