A novel role for KIFC1-MYH9 interaction in triple-negative breast cancer aggressiveness and racial disparity
View abstract on PubMed
Summary
This summary is machine-generated.African American women have higher triple-negative breast cancer (TNBC) risk. Nuclear kinesin C1 (KIFC1) drives TNBC progression and metastasis more strongly in African American patients, suggesting KIFC1 as a therapeutic target.
Area Of Science
- Oncology
- Molecular Biology
- Genetics
Background
- African American (AA) women face a higher incidence and more aggressive course of triple-negative breast cancer (TNBC) compared to European American (EA) women.
- There is a critical need for race-specific biomarkers to improve outcomes for AA TNBC patients.
- Kinesin family member C1 (KIFC1), a microtubule motor protein, is overexpressed in TNBC and linked to centrosome clustering and chromosomal instability.
Purpose Of The Study
- To investigate the race-specific role of nuclear KIFC1 (nKIFC1) in TNBC progression.
- To explore the interaction of nKIFC1 with myosin heavy chain 9 (MYH9) in AA TNBC cells.
- To evaluate KIFC1 as a potential therapeutic target for AA TNBC.
Main Methods
- Established homozygous KIFC1 knockout (KO) TNBC cell lines from AA and EA patients.
- Utilized RNA sequencing to analyze gene expression changes post-KIFC1 KO.
- Investigated the interaction between nKIFC1 and MYH9 in TNBC cells.
Main Results
- nKIFC1 interacted with MYH9 in AA TNBC cells, unlike in EA cells.
- KIFC1 KO significantly inhibited proliferation, migration, and invasion in AA TNBC cells but not EA TNBC cells.
- KIFC1 KO led to downregulation of cell migration, invasion, and metastasis genes in AA TNBC cells.
Conclusions
- The role of nKIFC1 in driving TNBC progression and metastasis is mechanistically stronger in AA patients than in EA patients.
- KIFC1 inhibition disrupted the KIFC1-MYH9 interaction and suppressed tumor progression in AA TNBC cells.
- KIFC1 represents a promising, race-specific therapeutic target for improving outcomes in African American patients with TNBC.
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