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CLEC12B suppresses lung cancer progression by inducing SHP-1 expression and inactivating the PI3K/AKT signaling

Decai Chi1, Dong Wang2, Minghui Zhang3

  • 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

Experimental Cell Research
|November 15, 2021
PubMed

Insights

This study reveals C-type lectin-like receptor 12B (CLEC12B) acts as a tumor suppressor in lung cancer. Overexpressing CLEC12B inhibits cancer cell growth and promotes apoptosis by regulating SHP-1 and the PI3K/AKT pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Lung cancer is a leading cause of cancer mortality globally.
  • C-type lectin-like receptor 12B (CLEC12B) is underexpressed in lung cancer tissues.
  • The precise function and mechanism of CLEC12B in lung cancer are not fully understood.

Purpose of the Study:

  • To investigate the role of CLEC12B in lung cancer progression.
  • To elucidate the molecular mechanisms underlying CLEC12B's function in lung cancer.
  • To determine the relationship between CLEC12B, SHP-1, and the PI3K/AKT pathway.

Main Methods:

  • Analysis of CLEC12B expression in lung cancer cells versus normal cells.
  • In vitro studies involving CLEC12B overexpression and knockdown to assess effects on cell viability, cell cycle, and apoptosis.
  • In vivo tumor xenograft models to evaluate CLEC12B's impact on tumor growth.
  • Co-immunoprecipitation and immunofluorescence assays to confirm protein interactions.
  • Western blotting to analyze protein expression and phosphorylation levels.

Main Results:

  • CLEC12B expression is significantly downregulated in lung cancer cells.
  • CLEC12B overexpression inhibits lung cancer cell proliferation, cell cycle progression, and promotes apoptosis by modulating Bcl-2 family proteins and caspase activation.
  • CLEC12B knockdown exhibits opposite effects, promoting proliferation and inhibiting apoptosis.
  • CLEC12B negatively regulates the PI3K/AKT signaling pathway by reducing PI3K-p85 and AKT phosphorylation.
  • CLEC12B interacts with and upregulates SHP-1, a phosphatase.
  • SHP-1 knockdown reverses the tumor-suppressive effects of CLEC12B.
  • In vivo, CLEC12B inhibits lung tumor growth, an effect reversible by CLEC12B inhibition.

Conclusions:

  • CLEC12B functions as a tumor suppressor gene in lung cancer.
  • CLEC12B exerts its tumor-suppressive effects by upregulating SHP-1 expression.
  • The mechanism involves the modulation of the PI3K/AKT signaling pathway.
  • CLEC12B represents a potential therapeutic target for lung cancer treatment.
Keywords:
CLEC12BCell behaviorLung cancerPI3K/AKTSHP-1

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