Jayanti, Melisa, Arnando, Mur'ah, Noviyanti

FUNCTIONAL ROLE OF VIMENTIN'S CYSTEINE IN XIST-MEDIATED EMT INHIBITION IN BREAST CANCER

Introduction

Functional role of vimentin's cysteine in xist-mediated emt inhibition in breast cancer. Investigate vimentin's C328 cysteine and its role in XIST-mediated EMT inhibition in breast cancer. This review reveals C328's tumor-suppressive function and its potential as a therapeutic target.

Abstract

Breast cancer is the most commonly diagnosed malignancy among women worldwide and a leading cause of cancer-related mortality, primarily due to its high metastatic potential. One mechanism underlying metastasis is the epithelial-to-mesenchymal transition (EMT), which enhances cancer cell mobility, invasiveness, and resistance to treatment. Vimentin, a type III intermediate filament protein, is a hallmark of EMT and plays a structural and regulatory role in cytoskeletal organization and cellular stress responses. Recent studies have highlighted the importance of a single cysteine residue at position 328 (C328) in vimentin, which functions as a redox-sensitive site influencing filament dynamics. However, the role of C328 in cancer progression remained largely unexplored. This literature review investigates the effect of a single amino acid substitution—C328 to serine (C328S)—on breast cancer cell behavior, focusing on findings published between 2020 and 2025, sourced from PubMed and Google Scholar. Evidence from MCF-7 breast cancer cell models reveals that expression of C328S-VIM induces morphological changes, cytoskeletal disorganization, and increased proliferation, migration, and invasion. Notably, C328S-VIM upregulates the long non-coding RNA XIST, which promotes EMT, estrogen independence, and stem-like properties. These findings indicate that the native C328 residue serves a tumor-suppressive function, partly through modulation of XIST activity. Overall, this review presents a novel insight into how a single amino acid mutation in vimentin can reprogram breast cancer cells toward a more aggressive and stem-like phenotype. The study highlights C328 as a potential therapeutic target and broadens our understanding of the molecular mechanisms driving breast cancer progression.

Review

This literature review addresses a critical area in breast cancer research, focusing on the under-explored functional role of a specific cysteine residue (C328) within the vimentin intermediate filament protein. Metastasis, driven by processes like epithelial-to-mesenchymal transition (EMT), remains the primary cause of breast cancer mortality. Vimentin, a well-established hallmark of EMT, has been implicated in cell mobility and invasiveness. This review's central premise, investigating how a single amino acid substitution (C328S) impacts breast cancer cell behavior, is both novel and highly significant, bridging the gap between subtle molecular changes and dramatic phenotypic shifts relevant to disease progression. Drawing on recent findings published between 2020 and 2025, the authors synthesize compelling evidence from MCF-7 breast cancer cell models. The review highlights that the C328S mutation in vimentin actively promotes an aggressive cancer phenotype, characterized by detrimental morphological changes, cytoskeletal disorganization, and markedly increased proliferation, migration, and invasion. Critically, the study elucidates a novel mechanistic link by demonstrating that C328S-VIM upregulates the long non-coding RNA XIST, which in turn fosters EMT, estrogen independence, and stem-like properties. This strongly supports the conclusion that the native C328 residue plays a crucial tumor-suppressive role, at least partly through its regulatory influence on XIST activity. The insights presented by this review are substantial, offering a nuanced understanding of how a discrete molecular alteration can profoundly reprogram breast cancer cells towards a more aggressive and treatment-resistant state. By pinpointing C328 as a key functional residue, the work not only broadens our knowledge of vimentin's intricate involvement in cancer progression but also identifies it as a promising novel therapeutic target. This comprehensive synthesis of recent literature makes a significant contribution to the field, paving the way for future experimental investigations into C328-modulating strategies to impede breast cancer metastasis.

Full Text

Comments

You need to be logged in to post a comment.