2. Academic Validation
  3. Calcium saccharate/DUSP6 suppresses renal cell carcinoma glycolytic metabolism and boosts sunitinib efficacy via the ERK-AKT pathway

Calcium saccharate/DUSP6 suppresses renal cell carcinoma glycolytic metabolism and boosts sunitinib efficacy via the ERK-AKT pathway

  • Biochem Pharmacol. 2024 Jun:224:116247. doi: 10.1016/j.bcp.2024.116247.
Huan Liu 1,  Longsheng Wang 2,  Xiaokai Shi 3,  Lei Yin 4,  Wei Zhai 1,  Shenglin Gao 5,  Yonghui Chen 6,  Tao Zhang 7
Affiliations

Affiliations

  • 1 Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Department of Urology, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, China; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 3 Department of Urology, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China.
  • 4 Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Urology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 5 Department of Urology, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China; Department of Urology, Gonghe County Hospital of Traditional Chinese Medicine, Qinghai, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, China. Electronic address: gaoshenglin12135@njmu.edu.cn.
  • 6 Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: cyh1488@163.com.
  • 7 Department of Urology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.. Electronic address: katanazt@126.com.
PMID: 38697311 DOI: 10.1016/j.bcp.2024.116247
Abstract

Current therapeutic options for renal cell carcinoma (RCC) are very limited, which is largely due to inadequate comprehension of molecular pathological mechanisms as well as RCC's resistance to chemotherapy. Dual-specificity Phosphatase 6 (DUSP6) has been associated with numerous human diseases. However, its role in RCC is not well understood. Here, we show that diminished DUSP6 expression is linked to RCC progression and unfavorable prognosis. Mechanistically, DUSP6 serves as a tumor suppressor in RCC by intervening the TAF10 and BSCL2 via the ERK-AKT pathway. Further, DUSP6 is also transcriptionally regulated by HNF-4a. Moreover, docking experiments have indicated that DUSP6 expression is enhanced when bound by Calcium saccharate, which also inhibits RCC cell proliferation, metabolic rewiring, and sunitinib resistance. In conclusion, our study identifies Calcium saccharate as a prospective pharmacological therapeutic approach for RCC.

Keywords

Calcium saccharate; DUSP6; HNF-4a; Renal cell carcinoma; Sunitinib.

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