Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function
2024

GCLM's Role in Colorectal Cancer Chemoresistance

Sample size: 406 publication 10 minutes Evidence: high

Author Information

Author(s): Lin Jin-Fei, Liu Ze-Xian, Chen Dong-Liang, Huang Ren-Ze, Cao Fen, Yu Kai, Li Ting, Mo Hai-Yu, Sheng Hui, Liang Zhi-Bing, Liao Kun, Han Yi, Li Shan-Shan, Zeng Zhao-Lei, Gao Song, Ju Huai-Qiang, Xu Rui-Hua

Primary Institution: Sun Yat-sen University Cancer Center, Guangzhou, PR China

Hypothesis

Does nuclear GCLM enhance chemoresistance in colorectal cancer through its interaction with NF-κB?

Conclusion

Nuclear GCLM promotes chemoresistance in colorectal cancer by enhancing NF-κB activity.

Supporting Evidence

  • GCLM depletion enhances the sensitivity of colorectal cancer cells to oxaliplatin.
  • Nuclear GCLM correlates with poor prognosis in colorectal cancer patients.
  • Phosphorylation of GCLM at T17 is crucial for its nuclear translocation.
  • Nuclear GCLM interacts with NKRF to enhance NF-κB activity.
  • High levels of nuclear GCLM are associated with reduced benefits from chemotherapy.

Takeaway

GCLM is a protein that helps cancer cells resist treatment, and when it moves to the nucleus, it makes the cancer harder to treat.

Methodology

The study utilized a CRISPR-Cas9 knockout library screen to identify the role of GCLM in chemoresistance, followed by in vitro and in vivo experiments.

Potential Biases

Potential bias in patient selection and the retrospective nature of clinical data analysis.

Limitations

The study primarily focuses on GCLM's role without exploring other potential factors influencing chemoresistance.

Participant Demographics

Patients with colorectal cancer from Sun Yat-sen University Cancer Center.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/s41467-024-55568-1

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