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.

PubMed
Abstract

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.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.4K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K