Rapamycin Treatment Correlates Changes in Primary Cilia Expression with Cell Cycle Regulation in Epithelial Cells

Maha H. Jamal, Chapman University
Ane C.F. Nunes, University of California, Irvine
Nosratola D. Vaziri, University of California, Irvine
Ramani Ramchandran, Medical College of Wisconsin
Robert L. Bacallao, Indiana University
Andromeda M. Nauli, Marshall B. Ketchum University
Surya M. Nauli, Chapman University

NOTICE: this is the author’s version of a work that was accepted for publication in Biochemical Pharmacology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochemical Pharmacology in 2020. https://doi.org/10.1016/j.bcp.2020.114056

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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.