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Updated: Oct 20, 2025
Visualization of G3BP Stress Granules Dynamics in Live Primary Cells
Published on: May 21, 2014
MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung
Haichang Li1, Pei-Hui Lin2, Pranav Gupta3
1Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, 43210, USA. Haichang.Li@osumc.edu.
Background:
Cancer cells develop resistance to chemotherapeutic intervention by excessive formation of stress granules (SGs), which are modulated by an oncogenic protein G3BP2. Selective control of G3BP2/SG signaling is a potential means to treat non-small cell lung cancer (NSCLC).
Methods:
Co-immunoprecipitation was conducted to identify the interaction of MG53 and G3BP2. Immunohistochemistry and live cell imaging were performed to visualize the subcellular expression or co-localization. We used shRNA to knock-down the expression MG53 or G3BP2 to test the cell migration and colony formation. The expression level of MG53 and G3BP2 in human NSCLC tissues was tested by western blot analysis. The ATO-induced oxidative stress model was used to examine the effect of rhMG53 on SG formation. Moue NSCLC allograft experiments were performed on wild type and transgenic mice with either knockout of MG53, or overexpression of MG53. Human NSCLC xenograft model in mice was used to evaluate the effect of MG53 overexpression on tumorigenesis.
Results:
We show that MG53, a member of the TRIM protein family (TRIM72), modulates G3BP2 activity to control lung cancer progression. Loss of MG53 results in the progressive development of lung cancer in mg53-/- mice. Transgenic mice with sustained elevation of MG53 in the bloodstream demonstrate reduced tumor growth following allograft transplantation of mouse NSCLC cells. Biochemical assay reveals physical interaction between G3BP2 and MG53 through the TRIM domain of MG53. Knockdown of MG53 enhances proliferation and migration of NSCLC cells, whereas reduced tumorigenicity is seen in NSCLC cells with knockdown of G3BP2 expression. The recombinant human MG53 (rhMG53) protein can enter the NSCLC cells to induce nuclear translation of G3BP2 and block arsenic trioxide-induced SG formation. The anti-proliferative effect of rhMG53 on NSCLC cells was abolished with knockout of G3BP2. rhMG53 can enhance sensitivity of NSCLC cells to undergo cell death upon treatment with cisplatin. Tailored induction of MG53 expression in NSCLC cells suppresses lung cancer growth via reduced SG formation in a xenograft model.
Conclusion:
Overall, these findings support the notion that MG53 functions as a tumor suppressor by targeting G3BP2/SG activity in NSCLCs.
Insights
MG53 acts as a tumor suppressor in non-small cell lung cancer (NSCLC) by inhibiting stress granule (SG) formation. This protein targets G3BP2/SG signaling, offering a potential therapeutic strategy for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) exhibits resistance to chemotherapy due to excessive stress granule (SG) formation.
- The oncogenic protein G3BP2 modulates SG formation, presenting a target for NSCLC treatment.
Purpose of the Study:
- To investigate the role of MG53 in non-small cell lung cancer (NSCLC) progression.
- To explore the potential of targeting the G3BP2/SG signaling pathway for NSCLC therapy.
Main Methods:
- Co-immunoprecipitation and immunohistochemistry to analyze MG53 and G3BP2 interactions and localization.
- shRNA-mediated knockdown and overexpression studies in mouse and human NSCLC models.
- In vivo experiments using xenograft and allograft models to assess tumorigenesis and therapeutic effects.
Main Results:
- MG53 interacts with G3BP2 and suppresses lung cancer progression; loss of MG53 accelerates lung cancer development.
- MG53 knockdown enhances NSCLC cell proliferation and migration, while G3BP2 knockdown reduces tumorigenicity.
- Recombinant human MG53 (rhMG53) inhibits SG formation, reduces tumor growth, and sensitizes NSCLC cells to chemotherapy.
Conclusions:
- MG53 functions as a tumor suppressor in NSCLC by modulating G3BP2/SG activity.
- Targeting MG53 or the G3BP2/SG pathway represents a promising therapeutic strategy for NSCLC.
