A Deregulated PI3K-AKT Signaling Pathway in Patients with Colorectal Cancer

Tao Zhang1, Yuanping Ma2, Jiansong Fang2

  • 1Department of Gastroenterology, Ruikang Hospital of Guangxi Traditional Chinese Medical University, No. 10 Hua Dong Road, Xingning District, Nanning, Guangxi, 530011, China. zhangtao41@aliyun.com.

Abstract

Insights

This study investigated gene alterations in the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway in colorectal cancer (CRC). Key genes were found to be deregulated, suggesting this pathway as a potential therapeutic target for CRC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway plays a crucial role in cell regulation.
  • Aberrant PI3K-AKT signaling is implicated in the development and progression of various cancers, including colorectal cancer (CRC).
  • Molecular targets within this pathway offer potential therapeutic strategies for CRC treatment.

Purpose of the Study:

  • To comprehensively profile gene expression alterations within the PI3K-AKT signaling pathway in colorectal cancer (CRC) patients.
  • To identify specific genes and their expression patterns associated with CRC tumoral tissue compared to healthy controls.
  • To explore the potential of the PI3K-AKT pathway as a therapeutic target for CRC.

Main Methods:

  • Gene expression profiling of 84 genes in the PI3K-AKT pathway using a polymerase chain reaction (PCR) array on tumoral and matched peritumoral tissues from 15 CRC patients.
  • Validation of array findings using real-time reverse transcription PCR for selected genes.
  • Confirmation of protein level changes for key genes using western blot (WB) analysis.

Main Results:

  • The PCR array identified 14 aberrantly expressed genes in CRC tumoral tissue, with 12 genes (e.g., CCND1, FOS, GSK3B) significantly upregulated and two genes (PDK1, PIK3CG) downregulated.
  • Real-time PCR validation confirmed the altered expression of CCND1, EIF4E, FOS, and PIK3CG.
  • Western blot analysis corroborated the upregulation of CCND1, EIF4E, FOS, and the downregulation of PIK3CG protein levels.

Conclusions:

  • The PI3K-AKT signaling pathway is significantly deregulated in colorectal cancer patients.
  • Identified gene alterations, particularly in CCND1, EIF4E, FOS, and PIK3CG, highlight the pathway's role in CRC pathogenesis.
  • The deregulated PI3K-AKT pathway presents potential therapeutic targets for colorectal cancer treatment.

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