PTPN14 functions as an oncogenic promoter in colon adenocarcinoma and liver hepatocellular carcinoma via Notch Signaling.

Protein tyrosine phosphatase non-receptor type 14 (PTPN14) exhibits dual roles in cancer, acting as either a tumor suppressor or oncogene depending on context, while its role in colon adenocarcinoma (COAD) and liver hepatocellular carcinoma (LIHC) remains unclear. Since COAD and LIHC showed high incidence and mortality rates, we investigated PTPN14's prognostic and mechanistic significance in COAD and LIHC. Pan-cancer analysis were performed based on TCGA and GEO database. Clinical validation used IHC staining of 50 COAD and 40 LIHC specimens. In vitro functional assays and in vivo xenograft models assessed PTPN14's impact on proliferation, migration, invasion and tumorigenicity. Mechanistic studies included Co-IP, immunofluorescence, ubiquitination assay and Western blot to evaluate PTPN14-Notch1 interaction and pathway regulation. As a result, pan-cancer analysis identified PTPN14 as prognostic biomarker in COAD and LIHC. Clinical validation confirmed PTPN14 as a prognostic biomarker in COAD and LIHC and associated with survival and TNM stage progression. In vitro experiments revealed knockdown of PTPN14 suppressed the proliferation, migration and invasion of COAD and LIHC cell lines. PTPN14 stabilized Notch1 by competitively binding to prevent FBXW7-mediated ubiquitination, and increasing the expression of Notch1 intracellular domain (Notch1 ICD) and downstream targets (DLL1 and HES1). At last, in vivo experiments revealed knockdown of PTPN14 inhibited xenograft tumor formation in COAD and LIHC cell lines. In conclusion, PTPN14 drives COAD and LIHC progression via Notch signaling stabilization, serving as a prognostic biomarker and potential therapeutic target for COAD and LIHC.