Abstract
Copy number alterations are crucial for gastric cancer (GC) development. In this study, Tocopherol alpha transfer protein-like (TTPAL) was identified to be highly amplified in our primary GC cohort (30/86). Multivariate analysis showed that high TTPAL expression was correlated with the poor prognosis of GC patients. Ectopic expression of TTPAL promoted GC cell proliferation, migration, and invasion in vitro and promoted murine xenograft tumor growth and lung metastasis in vivo. Conversely, silencing of TTPAL exerted significantly opposite effects in vitro. Moreover, RNA-sequencing and co-immunoprecipitation (Co-IP) followed by liquid chromatograph-mass spectrometry (LC-MS) identified that TTPAL exerted oncogenic functions via the interaction of Nicotinamide-N-methyl transferase (NNMT) and activated PI3K/AKT signaling pathway. Collectively, TTPAL plays a pivotal oncogenic role in gastric carcinogenesis through promoting PI3K/AKT pathway via cooperating with NNMT. TTPAL may serve as a prognostic biomarker of patients with GC.
Highlights
Gastric cancer (GC) represents an important global health problem
Multivariate Cox regression analysis showed that TTPAL expression was an independent poor prognostic factor for GC patients (RR = 1.831, 95% CI: 1.056–3.174, p = 0.031) (Fig. 1F)
We demonstrated that TTPAL was significantly upregulated in human GC at mRNA level and protein level
Summary
Gastric cancer (GC) represents an important global health problem. GC is the fifth commonest cancer worldwide and the third leading cause of cancer-related death [1].
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