Oncogenic Role of <scp>PTPN14</scp> in Pancreatic Cancer Through β‐Catenin/ <scp>NF</scp> ‐ <scp>κB</scp> Pathway Activation

Pancreatic cancer (PC) is one of the deadliest malignancies due to early metastasis, therapy resistance, and a highly immunosuppressive microenvironment. Although oncogenic mutations such as KRAS and TP53 are well characterized, the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14)-a Hippo-pathway regulator implicated in other cancers-remains unclear in PC. PTPN14 expression was analyzed in PC tissues and cell lines using immunohistochemistry and western blotting. Functional effects of PTPN14 knockdown or overexpression on proliferation, apoptosis, migration, and invasion were evaluated in vitro using CCK-8, flow cytometry, wound healing, and Transwell assays. Molecular mechanisms were explored via western blotting, immunofluorescence, and rescue experiments focusing on β-catenin and NF-κB signaling. In vivo, a xenograft mouse model assessed tumor growth, histopathology, apoptosis (TUNEL), Ki67 expression, and serum cytokine levels (ELISA). PTPN14 was markedly upregulated in PC tissues and cell lines. Silencing PTPN14 significantly inhibited cell proliferation, migration, and invasion, while enhancing apoptosis in vitro. Mechanistically, PTPN14 activated β-catenin and NF-κB signaling, promoting β-catenin nuclear translocation and p65 phosphorylation, with increased IL-6, TNF-α, and IL-1β secretion. In vivo, PTPN14 knockdown suppressed xenograft tumor growth, reduced Ki67 expression, enhanced apoptosis, and lowered serum pro-inflammatory cytokines. PTPN14 drives PC progression by co-activating β-catenin and NF-κB pathways and promoting a pro-tumor inflammatory milieu. These findings highlight PTPN14 as a promising therapeutic target to inhibit PC aggressiveness and inflammation-driven tumor progression.