2. Academic Validation
  3. TTPAL promotes gastric tumorigenesis by directly targeting NNMT to activate PI3K/AKT signaling

TTPAL promotes gastric tumorigenesis by directly targeting NNMT to activate PI3K/AKT signaling

  • Oncogene. 2021 Dec;40(49):6666-6679. doi: 10.1038/s41388-021-01838-x.
Wenxiu Liu  # 1 2,  Hongyan Gou  # 1 3,  Xiaohong Wang 1,  Xiaoming Li 2,  Xiaoxu Hu 1,  Hao Su 1,  Shengmian Li 4,  Jun Yu 5 6
Affiliations

Affiliations

  • 1 Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
  • 2 Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • 3 Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • 4 Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. shengmianli2013@163.com.
  • 5 Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. junyu@cuhk.edu.hk.
  • 6 Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. junyu@cuhk.edu.hk.
  • # Contributed equally.
PMID: 34642500 DOI: 10.1038/s41388-021-01838-x
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.

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