Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition.

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Complement component 3 (C3) is secreted by malignant epithelial cells.
• The precise mechanisms regulating C3 expression in tumor cells remain incompletely understood.
• Epithelial-mesenchymal transition (EMT) is a critical process in cancer progression and metastasis.

Purpose of the Study:

• To elucidate the regulatory mechanism of C3 expression in tumor cells.
• To investigate the role of C3 in mediating epithelial-mesenchymal transition (EMT).
• To explore the association between TWIST1, C3, and EMT in both pathological and physiological contexts.

Main Methods:

• Analysis of the C3 promoter region to identify regulatory elements.
• Investigation of transcription factor binding using chromatin immunoprecipitation assays.
• Assessment of E-cadherin expression and EMT markers in cancer cells.
• In vivo studies examining the colocalization of TWIST1 and C3 in tumors and embryonic tissues.

Main Results:

• TWIST1 was identified as a transcription factor that binds to the C3 promoter, enhancing C3 expression.
• C3 was found to decrease E-cadherin expression and promote EMT in cancer cells.
• C3-induced reduction in E-cadherin was dependent on C3a and Krüppel-like factor 5 (KLF5) in ovarian cancer cells.
• TWIST1 and C3 colocalized at invasive tumor edges and in specific embryonic structures (neural crest, limb buds).

Conclusions:

• TWIST1 is a key regulator of C3 expression in cancer cells.
• C3 actively promotes EMT and contributes to cancer cell invasiveness.
• The TWIST1-C3 axis plays a role in both pathological (cancer) and physiological (embryonic development) EMT processes.