2. Academic Validation
  3. ETHE1 dampens colorectal cancer angiogenesis by promoting TC45 Dephosphorylation of STAT3 to inhibit VEGF-A expression

ETHE1 dampens colorectal cancer angiogenesis by promoting TC45 Dephosphorylation of STAT3 to inhibit VEGF-A expression

  • Cell Death Dis. 2024 Aug 28;15(8):631. doi: 10.1038/s41419-024-07021-w.
Xiaowei She 1,  Jialu Xu 2,  Haokun Zhang 1,  Chengxin Yu 1,  Zejun Rao 1,  Jiakun Zhang 1,  Wenli Zhan 1,  Fuqing Hu 1,  Da Song 1,  Haijie Li 1,  Xuelai Luo 1,  Guihua Wang 1 3,  Junbo Hu 1,  Senyan Lai 4
Affiliations

Affiliations

  • 1 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 4 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. laisenyan@hust.edu.cn.
PMID: 39198402 DOI: 10.1038/s41419-024-07021-w
Abstract

Angiogenesis is critical for colorectal Cancer (CRC) progression, but its mechanisms remain unclear. Here, we reveal that ethylmalonic encephalopathy protein 1 (ETHE1), an essential Enzyme in hydrogen sulfide catabolism, inhibits VEGF-A expression and tumor angiogenesis in vitro and in vivo. Moreover, we find that this biological function of ETHE1 depends on the STAT3/VEGF-A pathway. Further investigation demonstrates that ETHE1 promotes the interaction between T cell protein tyrosine Phosphatase (TC45) and STAT3, resulting in decreased STAT3 phosphorylation and inhibition of the STAT3 signaling pathway. In clinical samples, we find that ETHE1 is downregulated in CRC and positively correlates with survival outcomes of CRC patients. Meanwhile, the negative correlation of ETHE1 and VEGF-A expression is verified in CRC specimens, and the patients with low ETHE1 and high VEGF-A expression exhibits poorer prognosis. Collectively, our study identifies ETHE1 as a novel regulator of tumor angiogenesis, implying its potential as a prognostic biomarker and promising antiangiogenic target for CRC patients.

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