TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.
Bottom Line: TMEPAI is constitutively and highly expressed in many types of cancer and is associated with poor prognosis.Knockdown of TMEPAI in Calu3 and NCI-H23 cells enhanced levels of Smad2 phosphorylation and significantly suppressed cell proliferation in the presence of TGF-β, indicating that highly expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells and reduces the growth inhibitory effects of TGF-β/Smad signaling.Together, these experiments indicate that TMEPAI promotes tumorigenic activities in lung cancer cells.
Affiliation: Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.Show MeSH
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Mentions: We next engineered stable knockdown of TMEPAI by two individual shRNAs (shTMEPAI#9 and shTMEPAI#10). These shRNAs significantly reduced TMEPAI expression in Calu3 cells (Calu3-sh#9 and Calu3-sh#10; Fig.3a). As a result, phosphorylated Smad2 levels were clearly enhanced (Fig.3b). Significantly stronger cell growth inhibition was obtained in Calu3-sh#9 and Calu3-sh#10 cells in the presence of 0.1 ng/mL TGF-β, and it was recovered by anti-TGF-β neutralizing antibodies (Fig.3c,d). Similar results were obtained with NCI-H23 cells (Fig. S3a–c).
Affiliation: Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.