Citrullination in Tumor Metastasis, Inside and Outside the Cells

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Tumor metastasis is a complex, multi-step process with poor prognosis, involving various cell types and the formation of a pre-metastatic niche (PMN).
• Protein citrullination, an irreversible post-translational modification catalyzed by peptidyl arginine deiminase (PADI), has emerged as a significant factor in cancer progression and metastasis.

Purpose of the Study:

• To review the multifaceted role of protein citrullination in cancer metastasis.
• To explore how citrullination contributes to the formation of the pre-metastatic niche (PMN).
• To discuss potential therapeutic strategies targeting protein citrullination for metastasis prevention.

Main Methods:

• Literature review of studies investigating protein citrullination in cancer.
• Analysis of the enzymatic activity of peptidyl arginine deiminase (PADI) and its substrates.
• Examination of the impact of intracellular and extracellular citrullination on metastasis.

Main Results:

• Intracellular citrullination of RNA polymerase and histones influences gene expression and genome structure.
• Extracellular citrullination contributes to creating a pro-metastatic environment, facilitating PMN formation.
• Protein citrullination is integral to the biological processes driving tumor cell dissemination.

Conclusions:

• Protein citrullination plays a critical role in enabling tumor metastasis, particularly in PMN development.
• Targeting PADI enzymes or leveraging anti-metastatic immune responses presents promising avenues for preventing cancer spread.