Granulin epithelin precursor promotes colorectal carcinogenesis by activating MARK/ERK pathway.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Granulin epithelin precursor (GEP) is a known growth factor implicated in various cancers.
• Its role in colorectal cancer (CRC) initiation and progression remains largely uncharacterized.

Purpose of the Study:

• To investigate the clinical significance of GEP in CRC.
• To elucidate the molecular mechanisms underlying GEP's function in CRC tumorigenesis.

Main Methods:

• GEP mRNA and protein expression analyzed in CRC cell lines and patient samples (n=190) via qRT-PCR and immunohistochemistry.
• Functional studies involved cell proliferation, invasion, migration assays, and in vivo xenograft models with GEP knockdown.
• Signaling pathway analysis utilized flow cytometry, western blot, and luciferase assays.

Main Results:

• GEP expression was significantly upregulated in CRC tissues compared to normal tissues.
• GEP overexpression correlated with advanced AJCC stage, metastasis, and poorer patient survival.
• GEP knockdown inhibited CRC cell proliferation, invasion, migration, induced cell cycle arrest and apoptosis, and suppressed tumor growth in vivo.
• GEP activation was linked to the MAPK/ERK signaling pathway.

Conclusions:

• GEP plays an oncogenic role in colorectal tumorigenesis through MAPK/ERK pathway activation.
• GEP represents a promising prognostic biomarker and therapeutic target for colorectal cancer.