Background: Serine/threonine kinase 33 (STK33) has been reported to play an important role in cancer cell proliferation. We investigated the role of STK33 in pancreatic neuroendocrine tumour (PNET) and the underlying mechanisms. Methods: PNET specimens and adjacent non-tumorous pancreatic tissues from 84 patients who underwent curative surgery for PNET were stained by immunochemistry for STK33. The relationships among STK33 expression, clinicopathological parameters and clinical prognosis were statistically analysed. MTT, scratching, Transwell and apoptosis assays were employed to detect the effects of STK33 knockdown (siSTK33) or STK33 overexpression (pSTK33) on major oncogenic properties of cells of 2 PNET cell lines (BON and QGP-1), and real-time PCR and western blot were used to examine the expression of relevant genes. Results: Relative to its expression in normal pancreatic tissue, STK33 was overexpressed in PNET specimens. Furthermore, STK33 expression was significantly associated with World Health Organization classification (p < 0.001), American Joint Committee on Cancer stage (p < 0.001), lymph node metastasis (p < 0.001), tumour size (p = 0.022), sex (p = 0.003), perineural invasion (p < 0.001) and shorter disease-free survival of patients with PNET (p < 0.001). Enforced STK33 expression promoted PNET cell proliferation, migration and invasion and tumour growth and inhibited cell apoptosis, whereas STK33 depletion exerted the opposite effects. Mechanistic studies revealed that STK33 promoted growth and progression of PNET via activation of the phosphotidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Conclusions: STK33 plays important roles in the tumour growth and progression of PNET via activation of the PI3K/AKT/mTOR pathway and has potential as a therapeutic target to improve PNET treatment.

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