2. Academic Validation
  3. AKR1C2 acts as a targetable oncogene in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

AKR1C2 acts as a targetable oncogene in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

  • J Cell Mol Med. 2020 Sep;24(17):9999-10012. doi: 10.1111/jcmm.15604.
Zhan-Fei Zhang 1,  Tie-Jun Huang 2,  Xin-Ke Zhang 3,  Yu-Jie Xie 4,  Si-Ting Lin 5,  Fei-Fei Luo 5,  Dong-Fang Meng 5,  Hao Hu 6,  Jing Wang 5,  Li-Xia Peng 5,  Chao-Nan Qian 2 7 8,  Chao Cheng 1,  Bi-Jun Huang 5
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
  • 2 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
  • 3 Department of Nuclear Medicine, The Second People's Hospital of Shenzhen, Shenzhen, China.
  • 4 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China.
  • 5 Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
  • 6 Department of Thoracic Surgery, The People's Hospital of Gaozhou, Maoming, China.
  • 7 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
  • 8 Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, China.
PMID: 32678482 DOI: 10.1111/jcmm.15604
Abstract

The aldo-keto reductases family 1 member C2 (AKR1C2) has critical roles in the tumorigenesis and progression of malignant tumours. However, it was also discovered to have ambiguous functions in multiple cancers and till present, its clinical significance and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) has been unclear. The aim of this study was to explore the role of AKR1C2 in the tumorigenesis of ESCC. Here, we showed that AKR1C2 expression was found to be up-regulated in ESCC tissues and was significantly associated with pathological stage, lymph node metastasis and worse outcomes. Functional assays demonstrated that an ectopic expression of AKR1C2 in ESCC cells resulted in increased proliferation, migration and cisplatin resistance, while knockdown led to inversing effects. Bioinformation analyses and mechanistic studies demonstrated that AKR1C2 activated the PI3K/Akt signalling pathway, furthermore, the inhibitor of PI3K or the selective inhibitor of AKR1C2 Enzyme activity could reverse the aggressiveness and showed synergistic antitumour effect when combined with cisplatin, both in vitro and in vivo. In conclusion, Our findings revealed that AKR1C2 could function as an oncogene by activating the PI3K/Akt pathway, as a novel prognostic biomarker and/or as a potential therapeutic target to ESCC.

Keywords

AKR1C2; PI3K/AKT signalling pathway; cisplatin resistance; combination therapy; oesophageal squamous cell carcinoma.

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