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Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients.

ABSTRACT: Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with normal pancreas tissues. STYK1 level was positively correlated with lymph node metastasis and clinical stage in pancreatic cancer patients. E-cadherin expression was inversely correlated with STYK1 expression in pancreatic cancer tissue samples. Patients with high STYK1 and low E-cadherin expression had the worst prognosis. In addition, STYK1 knockdown in pancreatic cancer cell lines inhibited cell proliferation, enhanced cell apoptosis, induced cell cycle arrest, and prohibited cell migration, while STYK1 over-expression showed the opposite effects. Silencing STYK1 also increased E-cadherin expression and inhibited epithelial-to-mesenchymal transition (EMT) and p-p38 expression in vitro. Over-expression had showed the opposite trends, and treatment with p38 inhibitor, SB203580, could reverse the trends. Thus, STYK1 repressed E-cadherin expression and promoted EMT, mediated by p38 MAPK signaling pathway, which was the possible mechanism for STYK1-mediated pancreatic cancer cell proliferation and migration. In summary, our results showed that STYK1 might be a prognostic marker for pancreatic cancer patients and might be a novel strategy for the treatment of pancreatic cancer.

SUBMITTER: Chen L

PROVIDER: S-EPMC5762325 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients.

Chen Luguang L Ma Chao C Bian Yun Y Shao Chengwei C Wang Tiegong T Li Jing J Chong Xiaodan X Su Li L Lu Jianping J

Oncotarget 20171130 67

Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with norm ...[more]

PMID: 29340057

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Project description:Pancreatic cancer is one of the most aggressive cancers worldwide with a high mortality rate. Prognosis remains poor even in this era of advanced medicine mainly due to early metastasis and invasion. The present study aimed to explore and validate predictors of distant metastasis and prognosis in pancreatic cancer. In our preliminary experiment, we established a novel metastatic pancreatic cancer cell line BxPC‑M8 from parent BxPC‑3 cells. Via whole genome sequencing, RT‑qPCR, western blotting, migration and invasion assays, we initially found that BxPC‑M8 shared similar biological characteristics to BxPC‑3, but only differed in enhanced metastatic and invasive capabilities with a significant increase in collagen type VI α1 chain (COL6A1) expression. Knockdown of COL6A1 via small interfering RNA led to a significant decrease in migration and invasion of BxPC‑M8 cells, suggesting suppressed epithelial‑mesenchymal transition. Furthermore, a significant increase in COL6A1 expression was observed in cancerous tissue compared with paracancerous tissue (40.7 vs 3.7, P=0.001). Additionally, its expression was observed to be significantly associated with distant metastasis and vascular invasion at the time of surgery. Multivariate analysis revealed that COL6A1 expression (hazard ratio 1.90, 95% confidence interval 1.04‑3.47, P=0.037) is an independent predictor of overall survival (OS). The median OS observed for COL6A1+ and COL6A1‑ patients was found to be 8±4 and 14±7 months (P=0.021), respectively. Of note, we identified that COL6A1 expression in tissue samples was associated with significantly reduced OS (P=0.001), demonstrating that COL6A1 may serve an important role in the metastatic process and could be considered as a predictor of poor outcomes in patients with pancreatic cancer. In addition, our findings suggest that COL6A1 could be an indicator of distant metastasis and a valid prognostic predictor in such patients; however, further investigation is required.

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Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients.

Publications

Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients.

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