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  3. TGM2-Mediated Autophagy Contributes to the Radio-Resistance of Non-Small Cell Lung Cancer Stem-like Cells

TGM2-Mediated Autophagy Contributes to the Radio-Resistance of Non-Small Cell Lung Cancer Stem-like Cells

  • Biomedicines. 2024 Sep 30;12(10):2231. doi: 10.3390/biomedicines12102231.
Qian Wang 1 2,  Qiuning Zhang 2 3,  Xiaohu Wang 1 2,  Hongtao Luo 2 3,  Tianqi Du 1 2,  Luyao Wu 2 3,  Mingyu Tan 1 2,  Yanliang Chen 1 2,  Xun Wu 1 2,  Shilong Sun 2 3,  Zhiqiang Liu 2 3,  Yi Xie 2 3,  Wenzhen Yuan 1
Affiliations

Affiliations

  • 1 The First School of Clinical Medicine, Lanzhou University, Lanzhou 730030, China.
  • 2 Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730030, China.
  • 3 Graduate School of the Chinese Academy of Sciences, Beijing 101499, China.
PMID: 39457544 DOI: 10.3390/biomedicines12102231
Abstract

Objectives: Cancer cells with 'stemness' are generally resistant to chemoradiotherapy. This study aims to compare the differences in radiation sensitivity of A549 and CD44+A549 stem-like cells to X-rays and carbon ion radiation (C-ions), and to find a target that can kill Cancer stem-like cells (CSCs) of non-small cell lung Cancer (NSCLC). Methods: The study used two cell lines (A549 and CD44+A549). The tumorigenicity of cells was tested with animal experiments. The cells were irradiated with X-rays and C-ions. Cell viability was detected using the CCK-8 and EdU assay. A liquid chromatograph-mass spectrometer (LC-MS) helped detect metabolic differences. Protein and mRNA expression were detected using a Western blot, reverse transcription-quantitative (RT-qPCR), and PCR array. The autophagic activity was monitored with a CYTO-ID® Autophagy Detection Kit 2.0. Immunofluorescence and co-immunoprecipitation helped to observe the localization and interaction relationships. Results: First, we verified the radio-resistance of CD44+A549 stem-like cells. LC-MS indicated the difference in Autophagy between the two cells, followed by establishing a correlation between the radio-resistance and Autophagy. Subsequently, the PCR array proved that TGM2 is significantly upregulated in CD44+A549 stem-like cells. Moreover, the TGM2 knockdown by small interfering RNA could decrease the radio-resistance of CD44+A549 cells. Bioinformatic analyses and experiments showed that TGM2 is correlated with the expression of CD44 and LC3B. Additionally, TGM2 could directly interact with LC3B. Conclusions: We established the CD44-TGM2-LC3 axis: CD44 mediates radio-resistance of CD44+A549 stem-like cells through TGM2 regulation of Autophagy. Our study may provide new biomarkers and strategies to alleviate the radio-resistance of CSCs in NSCLC.

Keywords

CD44; autophagy; cancer stem-like cells; non-small cell lung cancer; radiation sensitivity; transglutaminase 2.

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