Type VIIa1 collagen and laminin-γ2 promote a p53 mutant/HIF-1–dependent proinvasive phenotype. Type VIIa1 collagen and laminin-γ2 promote a p53 mutant/HIF-1–dependent.

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Type VIIa1 collagen and laminin-γ2 promote a p53 mutant/HIF-1–dependent proinvasive phenotype. Type VIIa1 collagen and laminin-γ2 promote a p53 mutant/HIF-1–dependent proinvasive phenotype. (A and B) p53 mutants affect hypoxia-mediated migration and invasion of NCI-H1155 and NCI-H23 NSCLC cells, and overexpression of type VIIa1 collagen and laminin-γ2 reverts this impairment. CTR, control; pCMV6, empty vector-transfected control cells. *P < 0.05, **P < 0.02; two-tailed paired t test. Error bars indicate the SE of independent biological replicates (n = 5 for NCI-H1155, n = 3 for NCI-H23). (C) Conditioned media (CM) from corresponding p53 mutant silenced cells treated for 24 h with 1% oxygen alter the migration and invasion capacity of NCI-H1155 and NCI-H23 NSCLC cells. *P < 0.05, **P < 0.01; two-tailed paired t test. Error bars indicate the SE of independent biological replicates (n = 4 for NCI-H1155, n = 3 for NCI-H23). (D) Western blot analysis of NCI-H1155 cells stably overexpressing type VIIa1 collagen or laminin-γ2 displays hyperactivation of pAKT T308. EV, empty vector; MW, molecular weight (molecular mass). (E) Proliferation doublings of NCI-H1155 cells stably overexpressing type VIIa1 collagen or laminin-γ2. *P < 0.05, **P < 0.01; paired two-tailed t test. Error bars indicate the SE of independent biological replicates (n = 4). Ivano Amelio et al. PNAS doi:10.1073/pnas.1808314115 ©2018 by National Academy of Sciences