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Updated: Oct 17, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
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Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

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

Wenxiu Liu1,2, Hongyan Gou1,3, Xiaohong Wang1

  • 1Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.

Oncogene
|October 13, 2021
PubMed

Insights

Tocopherol alpha transfer protein-like (TTPAL) amplification drives gastric cancer (GC) progression. High TTPAL expression correlates with poor prognosis and promotes tumor growth and metastasis by activating the PI3K/AKT pathway with NNMT.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Copy number alterations are key drivers in gastric cancer (GC) development.
  • Tocopherol alpha transfer protein-like (TTPAL) gene amplification is observed in a significant portion of primary GC.
  • Understanding the role of TTPAL in GC pathogenesis is crucial for identifying new therapeutic targets.

Purpose of the Study:

  • To investigate the oncogenic role of TTPAL in gastric cancer.
  • To elucidate the molecular mechanisms by which TTPAL promotes GC progression.
  • To evaluate TTPAL as a potential prognostic biomarker for GC patients.

Main Methods:

  • Analysis of TTPAL amplification in a primary GC cohort.
  • In vitro and in vivo experiments assessing the functional impact of TTPAL expression (ectopic expression and silencing).
  • RNA-sequencing, co-immunoprecipitation (Co-IP), and liquid chromatograph-mass spectrometry (LC-MS) to identify interacting proteins and signaling pathways.

Main Results:

  • High TTPAL amplification and expression were significantly correlated with poor prognosis in GC patients.
  • Ectopic TTPAL expression enhanced GC cell proliferation, migration, and invasion in vitro, and promoted tumor growth and lung metastasis in vivo.
  • Silencing TTPAL reversed these oncogenic effects.
  • TTPAL was found to interact with Nicotinamide-N-methyl transferase (NNMT), activating the PI3K/AKT signaling pathway.

Conclusions:

  • TTPAL plays a critical oncogenic role in gastric carcinogenesis.
  • TTPAL promotes GC progression by activating the PI3K/AKT pathway through cooperation with NNMT.
  • TTPAL represents a promising prognostic biomarker for gastric cancer.

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