RT Journal Article SR Electronic T1 ADAP1 promotes invasive squamous cell carcinoma progression and predicts patient survival JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900582 DO 10.26508/lsa.201900582 VO 2 IS 6 A1 Avery Van Duzer A1 Sachiko Taniguchi A1 Ajit Elhance A1 Takahiro Tsujikawa A1 Naoki Oshimori YR 2019 UL https://www.life-science-alliance.org/content/2/6/e201900582.abstract 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.