New Insights on the Progesterone (P4) and PGRMC1/NENF Complex Interactions in Colorectal Cancer Progression

Area of Science:

• Molecular Oncology
• Gastroenterology
• Endocrinology

Background:

• The role of hormone therapy (HT) in colorectal cancer (CRC) risk remains unclear.
• The specific mechanisms of progesterone (P4) and its receptors in CRC are not fully understood.
• Existing literature shows inconclusive data on hormone therapy and colorectal cancer risk.

Purpose of the Study:

• To investigate the expression of progesterone receptors (nuclear PGR and membrane PGRMC1) and NENF in CRC tissues.
• To analyze the effects of P4 and NENF on colorectal cancer cell proliferation and invasion.
• To explore the potential of NENF as a circulating biomarker for CRC.

Main Methods:

• Characterization of nuclear and membrane progesterone receptor expression in CRC tissues.
• Treatment of DLD-1 and HT-29 colorectal cancer cells with P4 and NENF.
• Analysis of cell proliferation, invasion, and protein co-localization (PGRMC1 and NENF) using immunocytochemistry.
• Measurement of serum NENF and IL-8 levels in CRC patients and controls.

Main Results:

• Abundant expression of PGRMC1 and NENF, with weak PGR expression, was observed in CRC tissues.
• P4 treatment stimulated CRC cell proliferation, while co-treatment with P4 and NENF significantly increased cell invasion, dependent on PGRMC1.
• Serum NENF levels were elevated in CRC patients, and P4/NENF treatment increased IL-8 release, suggesting a role in CRC progression and potential as a biomarker.

Conclusions:

• PGRMC1 and NENF play significant roles in colorectal cancer progression through non-classical P4 signaling.
• NENF may act as a co-activator for PGRMC1 in P4-mediated signaling pathways.
• NENF shows potential as a circulating biomarker for distinguishing CRC patients from healthy individuals.