NudCD1 affects renal cell carcinoma through regulating LIS1/Dynein signaling pathway

Am J Transl Res. 2018 Feb 15;10(2):519-524. eCollection 2018.

Abstract

Renal cell carcinoma (RCC) is one of the most common malignant tumors in urogenital system with an incidence accounting for about 3% of the whole body malignant tumor. NudC domain containing 1 (NudCD1), a new member of NudC family distributed in nucleus, is found to be upregulated in multiple tumors. However, its expression and role in RCC tissue has not been elucidated. NudCD1 expression in RCC tissue was measured by western blot and immunohistochemistry (IHC). NudCD1 level was elevated by overexpression vector to investigate its regulatory role on LIS1/Dynein signaling pathway. Cell morphology, intracellular localization, and cell division were observed by immunofluorescence together with delayed microscope photograph. The impact of NudCD1 overexpression on cell migration was assessed by Transwell assay. NudCD1 expression was significantly increased in RCC tissue compared with that in adjacent normal control. NudCD1/LIS1/Dynein signaling pathway was obviously upregulated in RCC tissue. Overexpression of NudCD1 level in A498 cell line markedly elevated NudCD1/LIS1/Dynein signaling pathway, suggesting they might be involved in RCC process. NudCD1 upregulation also caused abnormal microtubule fasciculus structure with multinuclear morphology, and promoted cell migration. NudCD1 expression was obviously increased in RCC and affected RCC cell division and migration possibly through activating NudCD1/LIS1/Dynein signaling pathway, indicating therapeutic targeting NudCD1 might be a new approach to inhibit RCC cell migration.

Keywords: LIS1/Dynein signaling pathway; NudCD1; Renal cell carcinoma; microtubulefasolculus; migration.