RNA sequence analysis of STYK1 knockdown in pancreatic cancer PANC-1 cells
Serine/threonine/tyrosine kinase 1 (STYK1), a proto-oncogenic transmembrane receptor alternatively termed NOK which consists of a kinase domain, intracellular domain, and transmembrane domain, was identified as an oncogene with high transformation potential in multiple cancer types. Recently, our group recognized that STYK1 depletion disrupts autophagosome biogenesis, establishing it as a critical modulator of autophagic flux. STYK1 was also reported as an oncogenic amplifier that hijacks KRAS effector networks, specifically the PI3K/AKT and MEK/ERK signaling axes, to drive tumor progression across malignancies. This molecular paradigm gains particular relevance in PDAC, where somatic KRAS mutations dominate (~95% prevalence) and functionally orchestrate pancreatic carcinogenesis from its earliest premalignant stages, notably during pancreatic intraepithelial neoplasia (PanIN) precursor lesions. This prompted a focused investigation into STYK1's functional implications within pancreatic cancer. By using multiple in vitro and in vivo assays, we figured out that higher STYK1 expression is related to poor pancreatic cancer survival and that STYK1 depletion suppresses pancreatic cancer cell development.To determine the molecular mechanism by which STYK1 promotes pancreatic cancer development, we performed RNA sequencing and found that STYK1 is involved in regulating the Wnt/ß-Catenin signaling pathway. We also elucidate a novel STYK1-driven mechanism for Wnt/ß-catenin activation in APC-independent pancreatic cancer and provide preclinical evidence for targeting STYK1-mediated signaling as a therapeutic strategy. Overall design: To investigate the molecular mechanism of STYK1 regulation in pancreatic cancer, we established the PANC-1 cell line of shSTYK1 using lentivirus. Total RNA was extracted for RNA sequencing.