CRISPLD1 promotes gastric cancer progression by regulating the Ca²⁺/PI3K-AKT signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Gastric cancer (GC) presents a significant global health challenge with a generally poor prognosis.
• Cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) has been implicated in tumor progression, but its specific role in GC remains largely undefined.

Purpose of the Study:

• To elucidate the pathogenic mechanism of CRISPLD1 in gastric cancer.
• To investigate the potential of CRISPLD1 as a therapeutic target for GC.

Main Methods:

• Analysis of public gene expression databases to correlate CRISPLD1 mRNA levels with GC patient data (prognosis, clinical stage).
• In vitro experiments involving CRISPLD1 knockdown in GC cells to assess effects on proliferation, invasion, and migration.
• Measurement of intracellular calcium levels and assessment of the PI3K-AKT signaling pathway activity following CRISPLD1 modulation.
• Pharmacological intervention using an AKT activator to evaluate its impact on GC cell behavior after CRISPLD1 knockdown.

Main Results:

• High CRISPLD1 mRNA expression in GC correlates with advanced T stage, increased overall survival events, and poorer prognosis.
• CRISPLD1 knockdown significantly inhibited GC cell proliferation, invasion, and migration.
• Downregulation of CRISPLD1 led to decreased intracellular calcium levels and suppressed the PI3K-AKT signaling pathway in GC cells.
• AKT pathway activation reversed the inhibitory effects of CRISPLD1 knockdown on GC cell migration and invasion.

Conclusions:

• CRISPLD1 promotes gastric cancer progression through the regulation of intracellular calcium levels and activation of the PI3K-AKT signaling pathway.
• CRISPLD1 represents a promising molecular target for the development of novel therapeutic strategies against gastric cancer.