Store-Operated Calcium Entry: Shaping the Transcriptional and Epigenetic Landscape in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) displays a particularly poor prognosis and low survival rate, mainly due to late diagnosis and high incidence of chemotherapy resistance. Genomic aberrations, together with changes in the epigenomic profile, elicit a shift in cellular signaling response and a transcriptional reprograming in pancreatic tumors. This endows them with malignant attributes that enable them to not only overcome chemotherapeutic challenges, but to also attain diverse oncogenic properties. In fact, certain genetic amplifications elicit a rewiring of calcium signaling, which can confer ER stress resistance to tumors while also aberrantly activating known drivers of oncogenic programs such as NFAT. While calcium is a well-known second messenger, the transcriptional programs driven by aberrant calcium signaling remain largely undescribed in pancreatic cancer. In this review, we focus on calcium-dependent signaling and its role in epigenetic programs and transcriptional regulation. We also briefly discuss genetic aberration events, exemplifying how genetic alterations can rewire cellular signaling cascades, including calcium-dependent ones.

Automated summary

PDAC has a poor prognosis and low survival rate due to late diagnosis and chemotherapy resistance. Genomic aberrations and epigenomic changes shift cellular signaling response in pancreatic tumors. Genetic amplifications can reroute calcium signaling and confer malignant attributes to tumors.