DAB2IP modulates primary cilia formation associated with renal tumorigenesis
| Autor: | Chun-Jung Lin, Jer Tsong Hsieh, Andrew Dang, Elizabeth Hernandez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
WT wild type Cancer Research Kinesins Con vector control medicine.disease_cause Mice 0302 clinical medicine Primary cilia DAB2IP DAB2 Interacting Protein C2 protein kinase C conserved region 2 domain PH Pleckstrin homology domain DAPI 4’ 6-diamidino-2-phenylindole Tumor suppressor gene ac-tubulin acetylated tubulin STR short tandem repeat Kidney qRT-PCR Quantitative real-time PCR Cilium lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kidney Neoplasms Renal cell carcinoma Cell biology medicine.anatomical_structure Cell Transformation Neoplastic UTSW University of Texas Southwestern Medical Center ras GTPase-Activating Proteins 030220 oncology & carcinogenesis Kinesin RCC renal cell carcinoma Disease Susceptibility Protein Binding Original article AIG anchorage independent growth assay Biology lcsh:RC254-282 DAB2IP Cell Line 03 medical and health sciences FBS fetal bovine serum Microtubule Ciliogenesis medicine Animals Humans KIF3A Cilia KD knockdown KO knockout ATCC American Type Culture Collection VHL von Hippel-Lindau 030104 developmental biology TCGA The Cancer Genome Atlas HIF hypoxia-inducible factors KIF3a kinesin family member 3A Carcinogenesis KIF3a IFT intraflagellar transport Protein Processing Post-Translational OE overexpression |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 1, Pp 169-180 (2021) Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 |
| Popis: | Primary cilium is a microtubule-based organelle that projects from the surfaces of most mammalian cell types and protrudes into the extracellular milieu as an antenna-like sensor to senses extracellular physical and biochemical signals, and then transmits signals into cytoplasm or nucleus to regulate numerous physical and developmental processes. Therefore, loss of primary cilia is associated to multiple cancer progression, including skin, breast, pancreas, ovarian, prostate, and kidney cancers. Our previous studies demonstrate that high prevalent loss of DAB2 Interacting Protein (DAB2IP) is associated with renal cell carcinoma, and we found a kinesin-like protein, kinesin family member 3A (KIF3a), was significantly increased in DAB2IP-interacting protein fraction. KIF3 is one of the most abundant kinesin-2 family proteins expressed in cells, and it is necessary for ciliogenesis. In this study, we observed that loss of DAB2IP in normal kidney epithelial cell significantly impair primary cilia formation. We unveiled a new mechanism of primary cilia stability via DAB2IP and KIF3a physical interaction at DAB2IP-PH domain. Furthermore, we found that KIF3a also act as a tumor suppressor in renal cell carcinoma, affect tumor development and patient survival. |
| Databáze: | OpenAIRE |
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