Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer

• Published in: Molecular oncology 2016-08, Vol.10 (7), p.1063-1077
• Main Authors: Joshi, Suhasini, Cruz, Eric, Rachagani, Satyanarayana, Guha, Sushovan, Brand, Randall E., Ponnusamy, Moorthy P., Kumar, Sushil, Batra, Surinder K.
• Format: Article
• Language: English
• Subjects: Acids; Animal models; Animals; Base Sequence; Bile; Bile acids; Bile Acids and Salts - pharmacology; Bilirubin; c-Jun; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cholecystectomy; Enzyme Activation - drug effects; FAK; Focal Adhesion Protein-Tyrosine Kinases - metabolism; FXR; Gallbladder diseases; Gene Expression Regulation, Neoplastic - drug effects; Jaundice; Kinases; Metastases; Metastasis; Mice, Transgenic; MUC4; Mucin-4 - metabolism; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Patients; Pheochromocytoma cells; Protein Transport - drug effects; Proto-Oncogene Proteins c-jun - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism; Signal Transduction - drug effects; Studies; Transcription activation; Transcription, Genetic - drug effects; Tumors; Up-Regulation - drug effects
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1016/j.molonc.2016.04.007

The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor-promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p