2. Academic Validation
  3. A novel tumor suppressor CECR2 down regulation links glutamine metabolism contributes tumor growth in laryngeal squamous cell carcinoma

A novel tumor suppressor CECR2 down regulation links glutamine metabolism contributes tumor growth in laryngeal squamous cell carcinoma

  • Clin Transl Oncol. 2021 Sep;23(9):1942-1954. doi: 10.1007/s12094-021-02603-y.
Xiaoting Wang  # 1 2,  Chong Xu  # 1 2,  Shengming Wang 1 2,  Weijun Huang 1 2,  Yuenan Liu 1 2,  Xiaoxu Zhang 1 2,  Niannian Li 1 2,  Zhenfei Gao 1 2,  Fan Wang 1 2,  Nan Zhang 3,  Jian Guan 1 2,  Hongliang Yi 4 5,  Feng Liu 6 7
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui, 200233, Shanghai, China.
  • 2 Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 200233, Shanghai, China.
  • 3 Department of Oncology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, Shandong, China.
  • 4 Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui, 200233, Shanghai, China. [email protected].
  • 5 Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 200233, Shanghai, China. [email protected].
  • 6 Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui, 200233, Shanghai, China. [email protected].
  • 7 Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 200233, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 33826083 DOI: 10.1007/s12094-021-02603-y
Abstract

Purpose: Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC).

Methods: Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model.

Results: Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG's effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression.

Conclusion: We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC.

Keywords

CECR2; Glutamine metabolism; Laryngeal squamous cell carcinoma; α-ketoglutarate.

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