Proinsulin Promotes Tumor Development in the PANC-1 Pancreatic Adenocarcinoma Cell Line

Area of Science:

• Oncology
• Endocrinology
• Molecular Biology

Background:

• Type 2 diabetes mellitus (T2DM) is a known risk factor for pancreatic ductal adenocarcinoma (PDAC).
• The precise mechanisms linking T2DM and PDAC remain largely unknown.
• Emerging evidence suggests a role for proinsulin, insulin's precursor, in cancer development.

Purpose of the Study:

• To investigate the potential tumorigenic effects of proinsulin in pancreatic ductal adenocarcinoma (PDAC).
• To explore the molecular pathways through which proinsulin influences PDAC progression.

Main Methods:

• Measured insulin receptor (IR) isoforms (IR-A, IR-B) in PDAC tissues and cell lines via RT-PCR.
• Assessed proinsulin's impact on ERK and AKT phosphorylation using Western blotting.
• Evaluated proinsulin's effects on cell proliferation, apoptosis resistance, and invasion.
• Utilized RNA sequencing to identify proinsulin-modulated genes.

Main Results:

• Insulin receptor isoform A (IR-A) was detected in PDAC tissues and cell lines.
• Proinsulin significantly enhanced ERK1/2 and AKT phosphorylation.
• Proinsulin promoted cell proliferation, inhibited apoptosis, and increased invasion.
• Proinsulin upregulated genes associated with proliferation, drug resistance, and invasion.

Conclusions:

• Proinsulin may promote PDAC progression.
• Binding to IR-A and subsequent activation of the ERK pathway is a proposed mechanism.
• These findings highlight a potential therapeutic target for PDAC in diabetic patients.