Calreticulin promotes EMT in pancreatic cancer via mediating Ca 2+ dependent acute and chronic endoplasmic reticulum stress

摘要: Background Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving oncogenic role of CRT PC. Methods potential regulating intracellular free Ca2+ dependent acute chronic endoplasmic reticulum stress (ERS)-induced EMT PC vitro vivo. Results Thapsigargin (TG) induced ERS increasing cells, which was reversed by silencing. Additionally, silencing inhibited TG-induced reversing changes key proteins signaling (ZO-1, E-cadherin Slug) ERK/MAPK (pERK). TG-promoted cell invasion migration also rescued but enhanced IRE1α (one stressors unfolded protein response). Meanwhile, co-immunoprecipitated co-localized with its led to upregulating independent IRE1-XBP1 axis. Moreover, silencing-promoted EMT, including inhibiting activation promotion mobility. In vivo, decreased subcutaneous tumor size distant liver metastasis following increase expression. A negative relationship between observed clinical samples, coordinately advanced stages poor prognosis patients. Conclusions promotes mediating IRE1α-mediated Slug