PMID- 33826083
OWN - NLM
STAT- MEDLINE
DCOM- 20211210
LR  - 20211214
IS  - 1699-3055 (Electronic)
IS  - 1699-048X (Linking)
VI  - 23
IP  - 9
DP  - 2021 Sep
TI  - A novel tumor suppressor CECR2 down regulation links glutamine metabolism 
      contributes tumor growth in laryngeal squamous cell carcinoma.
PG  - 1942-1954
LID - 10.1007/s12094-021-02603-y [doi]
AB  - 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 alphaKG supplementation. By transcriptomic 
      analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as 
      the downstream target gene for Gln and alphaKG. 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 alphaKG 
      supplementation could be magnified either, suggested that CECR2 feedback 
      suppressed Gln and alphaKG'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-alphaKG-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.
CI  - (c) 2021. Federacion de Sociedades Espanolas de Oncologia (FESEO).
FAU - Wang, Xiaoting
AU  - Wang X
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Xu, Chong
AU  - Xu C
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Wang, Shengming
AU  - Wang S
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Huang, Weijun
AU  - Huang W
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Liu, Yuenan
AU  - Liu Y
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Zhang, Xiaoxu
AU  - Zhang X
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Li, Niannian
AU  - Li N
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Gao, Zhenfei
AU  - Gao Z
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Wang, Fan
AU  - Wang F
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Zhang, Nan
AU  - Zhang N
AD  - Department of Oncology, Jinan Central Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, 250013, Shandong, China.
FAU - Guan, Jian
AU  - Guan J
AD  - 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.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China.
FAU - Yi, Hongliang
AU  - Yi H
AD  - 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. 
      yihongl@126.com.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China. yihongl@126.com.
FAU - Liu, Feng
AU  - Liu F
AUID- ORCID: 0000-0002-4442-7028
AD  - 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. 
      liufeng@sibs.ac.cn.
AD  - Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Road, Xuhui, 
      200233, Shanghai, China. liufeng@sibs.ac.cn.
LA  - eng
GR  - 81770988/National Natural Science Foundation of China/
GR  - 81970869/National Natural Science Foundation of China/
GR  - 81971240/National Natural Science Foundation of China/
GR  - 81770987/National Natural Science Foundation of China/
GR  - 18DZ2260200/Science and Technology Commission of Shanghai Municipality/
GR  - 201907018/Jinan science and technology development program/
GR  - 2017G006037/Key Technology Research and Development Program of Shandong/
PT  - Journal Article
DEP - 20210407
PL  - Italy
TA  - Clin Transl Oncol
JT  - Clinical & translational oncology : official publication of the Federation of 
      Spanish Oncology Societies and of the National Cancer Institute of Mexico
JID - 101247119
RN  - 0 (Cecr2 protein, human)
RN  - 0 (Ketoglutaric Acids)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Transcription Factors)
RN  - 0RH81L854J (Glutamine)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Cell Count
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/genetics
MH  - Disease Progression
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes, Tumor Suppressor
MH  - Glutamine/*metabolism/pharmacology
MH  - Humans
MH  - Ketoglutaric Acids/metabolism/pharmacology
MH  - Laryngeal Neoplasms/*genetics/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Middle Aged
MH  - Mitochondria/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Oxygen Consumption
MH  - Squamous Cell Carcinoma of Head and Neck/*genetics/metabolism/pathology
MH  - Transcription Factors/deficiency/*genetics/metabolism
OTO - NOTNLM
OT  - CECR2
OT  - Glutamine metabolism
OT  - Laryngeal squamous cell carcinoma
OT  - alpha-ketoglutarate
EDAT- 2021/04/08 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/04/07 12:34
PHST- 2021/02/09 00:00 [received]
PHST- 2021/03/18 00:00 [accepted]
PHST- 2021/04/08 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/04/07 12:34 [entrez]
AID - 10.1007/s12094-021-02603-y [pii]
AID - 10.1007/s12094-021-02603-y [doi]
PST - ppublish
SO  - Clin Transl Oncol. 2021 Sep;23(9):1942-1954. doi: 10.1007/s12094-021-02603-y. 
      Epub 2021 Apr 7.