Whole-genome screen identifies diverse pathways that negatively regulate ciliogenesis.

Molecular Biology of the Cell
Marion FaillerBrian D Dynlacht

Abstract

We performed a high-throughput whole-genome RNAi screen to identify novel inhibitors of ciliogenesis in normal and basal breast cancer cells. Our screen uncovered a previously undisclosed, extensive network of genes linking integrin signaling and cellular adhesion to the extracellular matrix (ECM) with inhibition of ciliation in both normal and cancer cells. Surprisingly, a cohort of genes encoding ECM proteins was also identified. We characterized several ciliation inhibitory genes and showed that their silencing was accompanied by altered cytoskeletal organization and induction of ciliation, which restricts cell growth and migration in normal and breast cancer cells. Conversely, supplying an integrin ligand, vitronectin, to the ECM rescued the enhanced ciliation observed on silencing this gene. Aberrant ciliation could also be suppressed through hyperactivation of the YAP/TAZ pathway, indicating a potential mechanistic basis for our findings. Our findings suggest an unanticipated reciprocal relationship between ciliation and cellular adhesion to the ECM and provide a resource that could vastly expand our understanding of controls involving "outside-in" and "inside-out" signaling that restrain cilium assembly.

References

Jun 1, 1996·Cellular Signalling·N Dhanasekaran, J M Dermott
Jul 10, 1999·The International Journal of Biochemistry & Cell Biology·I SchvartzS Shaltiel
Oct 31, 2000·Microscopy Research and Technique·A M Belkin, M A Stepp
May 31, 2001·The Journal of Biological Chemistry·B YanM H Ginsberg
Jul 13, 2001·The Journal of Cell Biology·P A Marignani, C L Carpenter
Sep 13, 2001·Proceedings of the National Academy of Sciences of the United States of America·T SørlieA L Børresen-Dale
Jan 24, 2004·Cancer Biology & Therapy·Louise R Howe, Anthony M C Brown
Jul 1, 2004·American Journal of Physiology. Renal Physiology·H A PraetoriusK R Spring
Mar 22, 2006·Cell Motility and the Cytoskeleton·Manuel ThéryMichel Bornens
May 3, 2006·The Journal of Cell Biology·Pirta Hotulainen, Pekka Lappalainen
May 3, 2006·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Susan R McGlashanC Anthony Poole
Jul 13, 2007·Immunological Reviews·Julio Gomez-RodriguezPamela L Schwartzberg
Aug 4, 2007·Experimental Cell Research·Kiran BhadrirajuChristopher S Chen
Oct 12, 2007·Journal of Cell Science·Stéphanie Pellegrin, Harry Mellor
Mar 18, 2008·Biochimica Et Biophysica Acta·Dorus A MansRachel H Giles
Aug 1, 2009·Nature Methods·Amanda BirminghamCaroline E Shamu
Apr 13, 2010·Current Biology : CB·Kimberly M McDermottGregory J Pazour
Apr 17, 2010·Nature Reviews. Genetics·Sarah C Goetz, Kathryn V Anderson
Jun 10, 2010·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Kun YuanAndra R Frost
Jun 3, 2011·The Journal of Clinical Investigation·Brian D LehmannJennifer A Pietenpol
Jul 24, 2012·Current Opinion in Cell Biology·Tamina Seeger-Nukpezah, Erica A Golemis
Nov 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kathirvel GopalakrishnanBina Joe
Jan 26, 2013·Genes & Development·Barbara E TanosMeng-Fu Bryan Tsou
Feb 8, 2013·Cell Cycle·Shubhra Majumder, Harold A Fisk
Jul 6, 2014·Cilia·Ina MenzlKimberly M McDermott
May 12, 2015·Frontiers in Bioscience (Landmark Edition)·Evette S Radisky, Derek C Radisky
Aug 21, 2015·Nature Communications·Sehyun KimBrian David Dynlacht
Feb 11, 2016·Oncotarget·Niamat Ali KhanJohannes V Swinnen
Feb 18, 2016·The Journal of Cell Biology·Hironori InabaMasaki Inagaki
Jun 29, 2016·Nature Cell Biology·Irma Sánchez, Brian David Dynlacht

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Citations

Aug 26, 2021·Open Biology·Yuhei NishimuraMasaki Inagaki

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