2. Academic Validation
  3. PTPN14 promotes gastric cancer progression by PI3KA/AKT/mTOR pathway

PTPN14 promotes gastric cancer progression by PI3KA/AKT/mTOR pathway

  • Cell Death Dis. 2023 Mar 10;14(3):188. doi: 10.1038/s41419-023-05712-4.
Hui Li 1 2 3,  Bingxin Guan 3,  Sen Liu 1 2,  Haiting Liu 1 2,  Lin Song 1 4,  Guohao Zhang 1 2,  Ruinan Zhao 1 2,  Chengjun Zhou 3,  Peng Gao 5 6
Affiliations

Affiliations

  • 1 Key Laboratory for Experimental Teratology of Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Shandong University, 250012, Jinan, Shandong, China.
  • 2 Department of Pathology, Qilu Hospital, Shandong University, 250012, Jinan, Shandong, China.
  • 3 Department of Pathology, The Second Hospital of Shandong University, 250012, Jinan, Shandong, China.
  • 4 Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250012, Jinan, Shandong, China.
  • 5 Key Laboratory for Experimental Teratology of Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Shandong University, 250012, Jinan, Shandong, China. gaopeng@sdu.edu.cn.
  • 6 Department of Pathology, Qilu Hospital, Shandong University, 250012, Jinan, Shandong, China. gaopeng@sdu.edu.cn.
PMID: 36898991 DOI: 10.1038/s41419-023-05712-4
Abstract

Gastric Cancer is a high molecular heterogeneous disease with a poor prognosis. Although gastric Cancer is a hot area of medical research, the mechanism of gastric Cancer occurrence and development is still unclear. New strategies for treating gastric Cancer need to be further explored. Protein tyrosine phosphatases play vital roles in Cancer. A growing stream of studies shows that strategies or inhibitors targeting Protein tyrosine phosphatases have been developed. PTPN14 belongs to the protein tyrosine Phosphatase subfamily. As an inert Phosphatase, PTPN14 has very poor activity and mainly functions as a binding protein through its FERM (four-point-one, ezrin, radixin, and moesin) domain or PPxY motif. The online database indicated that PTPN14 may be a poor prognostic factor for gastric Cancer. However, the function and underlying mechanism of PTPN14 in gastric Cancer remain unclear. We collected gastric Cancer tissues and detected the expression of PTPN14. We found that PTPN14 was elevated in gastric Cancer. Further correlation analysis indicated that PTPN14 was relevant with the T stage and cTNM (clinical tumor node metastasis classification) stage. The survival curve analysis showed that gastric Cancer patients with higher PTPN14 expression had a shorter survival time. In addition, we illustrated that CEBP/β (CCAAT enhanced binding protein beta) could transcriptionally activate PTPN14 expression in gastric Cancer. The highly expressed PTPN14 combined with NFkB (nuclear factor Kappa B) through its FERM domain and accelerated NFkB nucleus translocation. Then, NFkB promoted the transcription of PI3KA and initiated the PI3KA/Akt/mTOR pathway to promote gastric Cancer cell proliferation, migration, and invasion. Finally, we established mice models to validate the function and the molecular mechanism of PTPN14 in gastric Cancer. In summary, our results illustrated the function of PTPN14 in gastric Cancer and demonstrated the potential mechanisms. Our findings provide a theoretical basis to better understand the occurrence and development of gastric Cancer.

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