STIM1 overexpression in hypoxia microenvironment contributes to pancreatic carcinoma progression

Abstract

Objective: Stromal interaction molecule 1 (STIM1) overexpression has been reported to play an important role in progression ofseveral cancers. However, the mechanism of STIM1 overexpression and its relationship with hypoxia in pancreatic ductaladenocarcinoma (PDAC) remains unclear.

Methods: STIM1 and HIF-1α expression was tested using immunohistochemistry in tissue microarray (TMA) includingpancreatic cancer and matched normal pancreatic tissues, and their relationships with clinicopathological parameters werestatistically analyzed. q-PCR, Western blot, ChIP, and luciferase assay were employed to 030 analyze transcriptional regulationbetween HIF-1α and STIM1 in pancreatic cancer PANC-1 cells.

Results: Both STIM1 and HIF-1α showed higher positive rates and up-regulated expression in cancer tissues compared to that ofnormal tissues (P < 0.05). The Kaplan–Meier method revealed that higher HIF-1α and STIM1 expression levels were significantlycorrelated with decreased disease-free survival (P = 0.025 and P = 0.029, respectively). The expression of HIF-1α showed asignificant positive correlation with that of STIM1 in cancer tissues (rs = 0.3343, P = 0.0011) and pancreatic cancer cell lines.Furthermore, ChIP and luciferase assays confirmed that HIF-1α bound to the STIM1 promoter and regulated its expression inPANC-1 cells.

Conclusions: In hypoxia microenvironment, up-regulated expression of STIM1 mediated by HIF-1α promotes PDACprogression. HIF-1α and STIM1 are potential prognostic markers and/or therapeutic targets for PDAC treatment.