GOLPH3 inhibits erastin-induced ferroptosis in colorectal cancer cells

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Ferroptosis, a form of programmed cell death, is a potential therapeutic target for colorectal cancer (CRC).
• The precise mechanisms regulating ferroptosis in CRC remain incompletely understood.
• Identifying novel regulators of ferroptosis is crucial for developing effective CRC therapies.

Purpose of the Study:

• To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in regulating ferroptosis in colorectal cancer.
• To elucidate the molecular mechanisms by which GOLPH3 influences ferroptosis in CRC cells.

Main Methods:

• Analysis of GOLPH3 expression in human CRC tissues and cell lines.
• Manipulation of GOLPH3 expression (overexpression and knockdown) in CRC cell models (Caco-2 and HT-29).
• Assessment of ferroptosis induction using Erastin and evaluation of ferroptotic phenotypes.
• Investigation of protein-protein interactions and gene expression changes (PHB1, PHB2, NRF2).

Main Results:

• GOLPH3 was found to be overexpressed in CRC tissues and cell lines and correlated with ferroptosis-related gene expression.
• GOLPH3 overexpression reduced ferroptosis, while GOLPH3 knockdown enhanced ferroptosis in CRC cells.
• GOLPH3 induced prohibitin-1 (PHB1) and prohibitin-2 (PHB2) expression, inhibiting ferroptosis.
• GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2).

Conclusions:

• GOLPH3 functions as a negative regulator of ferroptosis in colorectal cancer.
• GOLPH3 confers resistance to ferroptosis in CRC cells through PHB1/PHB2 induction and interaction with PHB2/NRF2.
• Targeting GOLPH3 may represent a novel therapeutic strategy to enhance ferroptosis in CRC treatment.