DAB2IP modulates primary cilia formation associated with renal tumorigenesis

Chun Jung Lin, Andrew Dang, Elizabeth Hernandez, Jer Tsong Hsieh

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)169-180
Number of pages12
JournalNeoplasia (United States)
Volume23
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • DAB2IP
  • KIF3a
  • Primary cilia
  • Renal cell carcinoma
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Cancer Research

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