1. Academic Validation
  2. Nucleobindin-2 enhances the epithelial-mesenchymal transition in renal cell carcinoma

Nucleobindin-2 enhances the epithelial-mesenchymal transition in renal cell carcinoma

  • Oncol Lett. 2020 Jun;19(6):3653-3664. doi: 10.3892/ol.2020.11526.
Ran Tao 1 2 Wen-Bin Niu 3 Peng-Hui Dou 4 Shao-Bin Ni 1 Yi-Peng Yu 1 Li-Cheng Cai 1 Xin-Yuan Wang 1 Shu-Yi Li 5 Cheng Zhang 1 Zhen-Guo Luo 4
Affiliations

Affiliations

  • 1 Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
  • 2 Department of Urology, Shenzhen Luohu People's Hospital, Shenzhen, Guangdong 518000, P.R. China.
  • 3 Department of Urology, Shenzhen Samii Medical Center, Shenzhen, Guangdong 518000, P.R. China.
  • 4 Department of Urology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154001, P.R. China.
  • 5 Department of Pharmacy, University of California, San Diego, CA 92121, USA.
Abstract

Nucleobindin 2 (NUCB-2) is a multifunctional protein that contains several functional domains and is associated with a wide variety of biological processes, such as food intake and energy homeostasis. NUCB-2 has been demonstrated to be associated with worse malignant outcomes and cell migration in breast and prostate Cancer. However, to the best of our knowledge, its clinical and biological significance in renal cell carcinoma remains unknown. In the present study, tissue specimens from 68 patients with renal cell carcinoma and 10 normal controls were collected for NUCB-2 mRNA and protein assays. The NUCB-2 level in the patients with renal cell Cancer was significantly increased compared with the normal control patients. NUCB-2-knockout in the renal Cancer cell line SK-RC-52 inhibited migration and invasion. In addition, the expression levels of molecules associated with epithelial-mesenchymal transition (EMT), including E-cadherin, β-catenin, Slug and Twist, were affected by NUCB-2 suppression and the zinc finger E-box binding to homeobox 1 (ZEB1)-dependent pathway. The AMP-dependent protein kinase (AMPK)/target of rapamycin complex (mTORC) 1 signaling pathway participates in the regulation of NUCB-2-mediated metastasis and EMT. Suppression of NUCB-2 also inhibited tumor nodule formation in a murine renal cell carcinoma tumor model. In summary, NUCB-2 increased migration, invasion and EMT in renal cell carcinoma cells through the AMPK/TORC1/ZEB1 pathway in vitro and in vivo.

Keywords

adenosine monophosphate-dependent protein kinase; epithelial-mesenchymal transition; mammalian target of rapamycin complex 1; nucleobindin 2; renal cell carcinoma; zinc finger E-box-binding homeobox 1.

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