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Updated: Jun 2, 2025

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
KIF18A and CDK1 as combined therapeutic targets in cervical and endometrial carcinomas: based on bioinformatics
Mengjie Wang1, David Lukanovic2,3, Fabio Barra4,5
1Department of Pharmacy, Shaanxi Cancer Hospital, Xi'an, China.
Background:
Chromosomal instability (CIN) has been identified as a factor that increases the susceptibility of tumor cells to kinesin family member 18A (KIF18A) inhibitors. Limited research exists on genes that are associated with sensitization to KIF18A inhibitors (KIF18Ais). Our study aimed to identify a gene linked to heightened sensitivity to KIF18Ais in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and uterine corpus endometrial carcinoma (UCEC).
Methods:
The Cancer Genome Atlas (TCGA) and X2K Appyter databases were used to analyze potential kinases associated with KIF18A-related genes in CESC and UCEC. In vitro assessments, such as Cell Counting Kit-8 (CCK-8), transwell, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays, were performed to evaluate the combined effects of KIF18A and cyclin-dependent kinase 1 inhibitors (CDK1is) in CESC and UCEC cell lines.
Results:
Our findings indicated that the combination of KIF18A with kinases may potentially augment the efficacy of KIF18Ais, given its close involvement in cell cycle and chromosome segregation. Through bioinformatics analysis, we observed a significant up-regulation of CDK1 expression in CESC and UCEC, which exhibited a strong correlation with KIF18A expression. Our hypothesis regarding the potential of CDK1 as a combination therapeutic target for KIF18A was supported by our cell experiments, which demonstrated that inhibition of CDK1 notably increased the sensitivity of CESC and UCEC cells to KIF18Ais. The combined use of CDK1is and KIF18Ais exhibited a synergistic effect in inhibiting cell migration and inducing apoptosis in CESC and UCEC cells.
Conclusions:
This study provides evidence that targeting both KIF18A and CDK1 exerts synergistic anti-tumor effects in CESC and UCEC via inhibiting cell proliferation and migration and inducing apoptosis, suggesting a promising therapeutic strategy for these cancers.
Insights
Targeting kinesin family member 18A (KIF18A) and cyclin-dependent kinase 1 (CDK1) together shows synergistic anti-tumor effects in cervical and uterine cancers. This combination therapy inhibits proliferation and migration while inducing apoptosis, offering a promising strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Chromosomal instability (CIN) is linked to increased susceptibility to kinesin family member 18A inhibitors (KIF18Ais).
- Limited research exists on genes that sensitize tumors to KIF18Ais.
- This study focuses on identifying such a gene in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and uterine corpus endometrial carcinoma (UCEC).
Purpose of the Study:
- To identify a gene associated with heightened sensitivity to KIF18A inhibitors in CESC and UCEC.
- To investigate the potential of targeting KIF18A in combination with other kinases for cancer therapy.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and X2K Appyter databases for bioinformatics analysis.
- Performed in vitro assays including CCK-8, transwell, and TUNEL assays.
- Evaluated the combined effects of KIF18A and cyclin-dependent kinase 1 inhibitors (CDK1is) in CESC and UCEC cell lines.
Main Results:
- Observed significant upregulation of CDK1 expression in CESC and UCEC, correlating strongly with KIF18A expression.
- CDK1 inhibition increased sensitivity of CESC and UCEC cells to KIF18A inhibitors.
- Combined CDK1is and KIF18Ais demonstrated synergistic effects in inhibiting cell migration and inducing apoptosis.
Conclusions:
- Targeting both KIF18A and CDK1 exerts synergistic anti-tumor effects in CESC and UCEC.
- This dual targeting strategy inhibits tumor cell proliferation and migration while inducing apoptosis.
- The findings suggest a promising therapeutic strategy for CESC and UCEC.
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