1. Nucleobindin‑2 enhances the epithelial‑mesenchymal transition in renal cell carcinoma
- Author
-
Wen‑Bin Niu, Cheng Zhang, Li‑Cheng Cai, Shao‑Bin Ni, Shu‑Yi Li, Xin‑Yuan Wang, Peng‑Hui Dou, Yi‑Peng Yu, Ran Tao, and Zhen‑Guo Luo
- Subjects
0301 basic medicine ,renal cell carcinoma ,Cancer Research ,Cell ,epithelial-mesenchymal transition ,nucleobindin 2 ,mTORC1 ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,medicine ,Epithelial–mesenchymal transition ,Chemistry ,Cell migration ,Articles ,mammalian target of rapamycin complex 1 ,Cell cycle ,medicine.disease ,Nucleobindin 2 ,zinc finger E-box-binding homeobox 1 ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,adenosine monophosphate-dependent protein kinase - 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.
- Published
- 2020