Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway

Octamer-binding transcription factor 4 (OCT4) is one of the factors associated with self-renewal and differentiation in cancer stem cells, and is crucial for the progression of various types of human malignancy. However, the expression and function of OCT4 in human pancreatic cancer has not been fully elucidated. The purpose of the present study was to investigate the function and molecular mechanisms of OCT4 in pancreatic cancer cells. The clinical significance of OCT4 expression was assessed by an immunohistochemical assay using a tissue microarray procedure in pancreatic cancer tissues and cells with different degrees of differentiation. A loss-of-function approach was used to examine the effects of a lentivirus-mediated OCT4 small hairpin RNA vector on biological behaviors, including cell proliferative activity and invasive potential. The results demonstrated that the expression levels of OCT4 protein in cancer tissues were significantly elevated compared with those in adjacent non-cancerous tissues (65.0 vs. 42.5%; P=0.005), which was correlated with tumor differentiation (P=0.008). The knockdown of OCT4 inhibited the proliferation and invasion of pancreatic cancer cells (Panc-1) expressing high levels of OCT4, accompanied with decreased expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2). In conclusion, the present study reveals that the increased expression of OCT4 is correlated with the differentiation of pancreatic cancer, while knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of AKT pathway-mediated PCNA and MMP-2 expression, suggesting that OCT4 might serve as a potential therapeutic target for the treatment of pancreatic cancer.

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