Septin4 promotes cell death in human colon cancer cells by interacting with BAX

Xin Zhao1, Hao Feng2, Yang Wang3

  • 1Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, Collegeof Medical Science, China Medical University; Liaoning Province, Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, China.

Insights

Septin4, a tumor suppressor, is downregulated in colorectal cancer, promoting cell death and worsening prognosis. It interacts with BAX, enhancing Doxorubicin-induced cell death and ROS production.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Septin4 acts as a tumor suppressor by promoting apoptosis via XIAP antagonism.
  • Its role and binding partners in colorectal cancer (CRC) remain largely unexplored.

Purpose of the Study:

  • To investigate the role of Septin4 in colorectal cancer development and its interaction with BAX.
  • To explore Septin4's potential as a therapeutic target in CRC.

Main Methods:

  • Quantitative analysis of Septin4 expression in human colon cancer tissues.
  • In vitro studies using Septin4-overexpressing and knockdown colon cancer cell lines.
  • In vivo studies to assess Septin4's effect on tumor growth.

Main Results:

  • Septin4 expression is significantly lower in colon tumors than adjacent normal tissue, correlating with poor prognosis.
  • Septin4 overexpression enhances Doxorubicin (DOX)-induced apoptosis and ROS production.
  • Septin4 knockdown confers resistance to DOX-induced cell death and reduces ROS levels.
  • BAX identified as a novel Septin4 binding partner, with interaction enhanced by DOX.
  • Septin4 knockdown promotes colon cancer cell growth in vivo.

Conclusions:

  • Septin4 functions as a crucial tumor suppressor in colorectal cancer.
  • Septin4's interaction with BAX is vital for DOX-induced apoptosis.
  • Septin4 represents a promising target for novel colorectal cancer therapies.

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