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Updated: Nov 21, 2025

An Orthotopic Bladder Cancer Model for Gene Delivery Studies
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KNSTRN promotes tumorigenesis and gemcitabine resistance by activating AKT in bladder cancer

Yaoyi Xiong1, Lingao Ju2,3,4, Lushun Yuan5

  • 1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Oncogene
|January 16, 2021
PubMed

Insights

KNSTRN promotes bladder cancer by activating AKT phosphorylation, leading to increased malignancy and gemcitabine resistance. This oncogene may be a therapeutic target for bladder cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • KNSTRN, a mitotic spindle component, has been underexplored in tumorigenesis.
  • AKT signaling is crucial in cancer development, regulated by PTEN and phosphoinositide 3-kinase (PIP3).

Purpose of the Study:

  • To investigate the role of KNSTRN in bladder cancer progression and its mechanism of action.
  • To determine if KNSTRN influences AKT activation and chemoresistance.

Main Methods:

  • Correlation analysis between KNSTRN expression and bladder cancer malignancy.
  • Biochemical assays to study the interaction of KNSTRN, PTEN, and AKT at the cell membrane.
  • PIP3 pull-down assays to assess AKT translocation.
  • In vitro and in vivo experiments to evaluate the effect of KNSTRN on metastasis and gemcitabine resistance.
  • Experiments using AKT inhibitor MK2206 and AKT overexpression to validate findings.

Main Results:

  • KNSTRN expression positively correlates with bladder cancer malignancy.
  • KNSTRN activates AKT phosphorylation at Thr308 and Ser473 by promoting AKT movement to PIP3 and reducing PTEN suppression.
  • KNSTRN promotes bladder cancer cell metastasis and gemcitabine resistance.
  • Inhibition of AKT signaling or overexpression of AKT can reverse the effects of KNSTRN.

Conclusions:

  • KNSTRN acts as an oncogene in bladder cancer by activating AKT phosphorylation.
  • KNSTRN promotes tumor metastasis and chemoresistance, suggesting it as a potential therapeutic target for bladder cancer.

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