Ca2+是细胞生命活动的重要信使分子，而STIM1 是内质网膜上的Ca2+感受蛋白，能感知Ca2+的浓度，激活钙池操纵钙离子通道，引起细胞外Ca2+内流，因此STIM1 是细胞主动吸收Ca2+的重要分子，控制着细胞增殖、凋亡、粘附、运动。我们发现STIM1 在胰腺癌中表达增加，与患者预后不良密切相关，但其表达调控机制尚未阐明。乏氧是胰腺癌组织重要微环境，前期研究提示，乏氧诱导因子HIF 促进STIM1 的表达，推测乏氧条件下的HIF-1/STIM1/Ca2+/下游分子直接参与了胰腺癌的侵袭转移；我们还发现乏氧条件下ERK的活化增强，不仅促进HIF 的表达，而且进一步活化了STIM1。因此我们推测STIM1 的表达存在ERK/HIF/STIM1 调控环路和pERK/pSTIM1活化通路。本研究拟围绕着STIM1在胰腺癌乏氧微环境下的表达调控和活化机制，探讨其在胰腺癌侵袭中的地位和应用价值。

Calcium (Ca2+) is the important messenger of cellproliferation, differentiation and gene transcription, while stromal interaction molecule 1 (STIM1) located on the endoplasmic reticulum is calcium sensor and can perceive Ca2+ concentration. STIM1 can activate calcium -operated calcium channels and cause extracellular Ca2+ influx. Therefore, STIM1, as an important constituent molecules of calcium pool channel, plays an important role in cell mitosis, proliferation, apoptosis, secretion, adhesion and motility. We found that the expression of STIM1 was increased in pancreatic cancer cells, and its overexpression was corelated with poor prognosis of patients with PC, which may suggested STIM1 is one important molecular in the invasion and metastasis of pancreatic cancer cells. However, its expression regulation mechanism has not been elucidated. Hypoxia is one important microenvironment feature of pancreatic cancer. Our previous studies demonstrated that HIF can promote the expression of STIM1 under hypoxia suggesting the possible role of HIF-1/STIM1/Ca2+/ downstream function molecular involved in the invasion and metastasis of pancreatic cancer. We also found that, under hypoxic conditions, ERK activation was enhanced, which not only promoted the expression of HIF , but also activated STIM1. Therefore, we hypothesized that the presence of STIM1 expression regulation loop ERK/HIF/STIM1 and activation pathway pERK/pSTIM1. In this study, we will focus on the regulation mechanism and activation mechanism of STIM1 in pancreatic cancer under hypoxic microenvironment and explore its role in the invasion and metastasis of pancreatic cancer, and to explore its prognostic significance and clinical applications.