Fascin Drives Breast Cancer Cell Proliferation Partly by Modulating the Cell Cycle Checkpoint Regulators of the G1-S...

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Breast cancer (BC) remains a leading cause of cancer mortality globally, with relapse and metastasis posing significant challenges.
• Fascin, an actin-bundling protein, is known to promote BC progression and drug resistance, but its role in proliferation is unclear.

Purpose of the Study:

• To investigate the role of fascin in breast cancer cell proliferation and elucidate the underlying molecular mechanisms.
• To assess the clinical relevance of fascin expression in breast cancer patient samples.

Main Methods:

• Bioinformatics analysis of public BC datasets.
• Gene manipulation (gain and loss of function) in BC cell lines (SK-BR-3, MDA-MB-231).
• Flow cytometry, Western blots, Real-Time Cell Analyzer (RTCA).
• Immunohistochemistry on 68 BC patient samples.

Main Results:

• FSCN1 expression correlated significantly with proliferation signatures and cell cycle progression (G1-S phase) in BC datasets.
• Fascin overexpression enhanced proliferation in SK-BR-3 cells, while fascin silencing reduced proliferation in MDA-MB-231 cells.
• Fascin upregulated nuclear SKP2 and downregulated p27, key regulators of the G1-S cell cycle checkpoint.
• Clinical samples showed correlations between fascin, Ki-67, SKP2, and p27 expression.

Conclusions:

• Fascin acts as a key driver of the G1-S phase transition, promoting breast cancer cell proliferation.
• Targeting fascin may offer a novel therapeutic strategy for breast cancer.