Medical College of Wisconsin
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Rapamycin treatment correlates changes in primary cilia expression with cell cycle regulation in epithelial cells. Biochem Pharmacol 2020 08;178:114056

Date

05/30/2020

Pubmed ID

32470549

DOI

10.1016/j.bcp.2020.114056

Abstract

Primary cilia are sensory organelles that regulate cell cycle and signaling pathways. In addition to its association with cancer, dysfunction of primary cilia is responsible for the pathogenesis of polycystic kidney disease (PKD) and other ciliopathies. Because the association between cilia formation or length and cell cycle or division is poorly understood, we here evaluated their correlation in this study. Using Spectral Karyotyping (SKY) technique, we showed that PKD and the cancer/tumorigenic epithelial cells PC3, DU145, and NL20-TA were associated with abnormal ploidy. We also showed that PKD and the cancer epithelia were highly proliferative. Importantly, the cancer epithelial cells had a reduction in the presence and/or length of primary cilia relative to the normal kidney (NK) cells. We then used rapamycin to restore the expression and length of primary cilia in these cells. Our subsequent analyses indicated that both the presence and length of primary cilia were inversely correlated with cell proliferation. Collectively, our data suggest that restoring the presence and/or length of primary cilia may serve as a novel approach to inhibit cancer cell proliferation.

Author List

Jamal MH, Nunes ACF, Vaziri ND, Ramchandran R, Bacallao RL, Nauli AM, Nauli SM

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




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