Insulin receptor tyrosine kinase substrate (IRTKS) promotes the tumorigenesis of pancreatic cancer via PI3K/AKT signaling.

Abstract

Pancreatic cancer (PC) is a common type of tumor, which ranks for the seventh leading cause of cancer death worldwide. Insulin receptor tyrosine kinase substrate (IRTKS) plays an important regulatory role in cell proliferation, motility and survival. In this study, we explore the effect of IRTKS on the occurrence and development of PC. The expression and clinical features of IRTKS were predicted in database, PC cell lines and samples. IRTKS overexpressed and knocked down PC cell lines were established by lentivirus. CCK-8 assay, scratch migration assay and Transwell assay were used to analyze IRTKS oncogenic functions in cell lines. Bioinformatic enrichment analysis were conducted to explore the biological functions IRTKS involved in PC and Western Bolt assay was performed to reveal the downstream signaling molecules. It is detected that IRTKS is highly expressed in PC (P < 0.05), and overexpression of IRTKS predicted worse overall survival (OS, P = 0.018). The proliferation, migration and invasion ability were significantly enhanced in IRTKS overexpressed cells and inhibited in IRTKS knocked down cells (P < 0.05). Bioinformatic enrichment analysis based on GSE46583 dataset showed that IRTKS was significantly involved in PI3K/AKT pathway. Further investigation revealed that overexpression of IRTKS upregulated the ratio of p-PI3K/PI3K and p-AKT/AKT in vitro, while silencing of IRTKS presented opposite results, and PI3K inhibitor LY294002 treatment induced the phenotypic alteration of cell lines (P < 0.05). In conclusion, IRTKS plays an important role in PC tumorigenesis via PI3K/AKT pathway phosphorylated activation, and has a potential clinical application value in prognosis for PC.

• Authors: Yu Lu, Xin-Yuan Zhou, Cheng-Liang Zhou, Jie Liu, Tao Yong, Yong Fan, Chen Wang
• Journal: Human cell (Hum Cell) Vol. 35 Issue 6 Pg. 1885-1899 (Nov 2022) ISSN: 1749-0774 [Electronic] Japan
• PMID: 36057038 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s) under exclusive licence to Japan Human Cell Society.

Chemical References

• BAIAP2L1 protein, human
• Microfilament Proteins
• insulin receptor tyrosine kinase
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Carcinogenesis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Humans
• Microfilament Proteins
• Pancreatic Neoplasms (pathology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-akt (metabolism)
• Pancreatic Neoplasms