S100A14 promotes progression and gemcitabine resistance in pancreatic cancer

S100 calcium binding protein A14 (S100A14) plays an important role in the progression of several types of cancer. However, its roles in pancreatic ductal adenocarcinoma (PDAC) are largely unexplored. Here, we characterized the functional roles of S100A14 in the progression and chemoresistance of PDAC. Gene expression microarray identified that S100A14 was significantly highly expressed in four pairs of human PDAC tumor compared with corresponding non-tumor tissues genes. Quantitative reverse transcription PCR (qRT-PCR), western blotting and immunohistochemical staining (IHC) showed that S100A14 was frequently overexpressed in PDAC cell lines and tissues. Moreover, expression level of S100A14 was positively correlated to advanced cancer stages. Further, Kaplan-Meier survival analysis suggested that PDAC patients with low S100A14 expression had longer overall survival in TCGA PDAC datasets. Transient overexpressing of S100A14 promoted cell proliferation, anchorage-independent colony formation, cell migration and invasion in cell lines with low endogenous S100A14 levels, while transient silencing of S100A14 inhibited cell proliferation, anchorage-independent colony formation, cell migration and invasion in cell lines with high endogenous S100A14 levels. Persistent knockdown of S100A14 by transducing shRNAs carrying lentivirus inhibited subcutaneous tumor formation in nude mice, and sensitized the PDAC cells to gemcitabine treatment. Taken together, S100A14 exhibited oncogenic properties by promoting cell proliferation, transformation, migration and invasion, and enhanced in vivo tumor growth. More importantly, inhibition of S100A14 could effectively abrogate the cancerous properties of the PDAC cells. Our study indicated that S100A14 was a valuable target for the development of therapeutic strategy, as well as a diagnostic and prognosis biomarker for PDAC patients. (C) 2021 Published by Elsevier B.V. on behalf of IAP and EPC.

Automated summary

S100A14 is highly expressed in PDAC and associated with tumor progression and chemoresistance. Targeting S100A14 could effectively inhibit the cancerous properties of PDAC cells, making it a valuable target for therapeutic strategies.