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Updated: Nov 9, 2025

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
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AIM2 Inhibits BRAF-Mutant Colorectal Cancer Growth in a Caspase-1-Dependent Manner

Shailendra Shah1, Shaolan Qin2, Yang Luo2

  • 1Department of Surgery, Patan Hospital, Patan Academy of Health Sciences, Lalitpur, Nepal.

Frontiers in Cell and Developmental Biology
|April 12, 2021
PubMed

Insights

Absent in melanoma 2 (AIM2) is downregulated in BRAF-mutant colorectal cancer (CRC). Restoring AIM2 inhibits tumor growth and metastasis by inducing caspase-1-dependent necrotic cell death, offering new therapeutic strategies for CRC.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Absent in melanoma 2 (AIM2) is a DNA sensor involved in innate immunity.
  • AIM2's role in BRAF-mutant colorectal cancer (CRC) pathogenesis is not well understood.
  • Understanding AIM2's function in BRAF-mutant CRC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the expression level of AIM2 in BRAF-mutant CRC.
  • To elucidate the functional role and underlying mechanisms of AIM2 in BRAF-mutant CRC cell growth and progression.
  • To evaluate the therapeutic potential of AIM2 in preclinical models of BRAF-mutant CRC.

Main Methods:

  • Analysis of AIM2 expression in BRAF-mutant versus wild-type CRC tumor tissues.
  • In vitro studies involving AIM2 overexpression in CRC cells, including cell viability, cell death detection, and caspase activity assays.
  • In vivo evaluation of AIM2's antitumor effects using cell-derived tumor xenograft (CDX) models and patient-derived organoids (PDOs).

Main Results:

  • AIM2 expression was found to be lower in BRAF-mutant CRC tissues compared to BRAF wild-type tissues.
  • Overexpression of AIM2 significantly inhibited BRAF-mutant CRC cell viability and induced necrotic cell death.
  • AIM2-mediated cell death was dependent on caspase-1 activation.
  • AIM2 overexpression demonstrated significant antitumor and anti-metastatic effects in vivo and in PDO models.

Conclusions:

  • AIM2 acts as a tumor suppressor in BRAF-mutant CRC.
  • AIM2 inhibits BRAF-mutant colon cancer growth and metastasis via a caspase-1-dependent pathway.
  • AIM2 represents a potential therapeutic target for BRAF-mutant CRC.
Keywords:
BRAF-mutantabsent in melanoma 2caspase-1colorectal cancerpatient-derived organoids

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