• This record comes from PubMed

The toxic effect of cytostatics on primary cilia frequency and multiciliation

. 2019 Aug ; 23 (8) : 5728-5736. [epub] 20190617

Language English Country England, Great Britain Media print-electronic

Document type Journal Article, Research Support, Non-U.S. Gov't

The primary cilium is considered as a key component of morphological cellular stability. However, cancer cells are notorious for lacking primary cilia in most cases, depending upon the tumour type. Previous reports have shown the effect of starvation and cytostatics on ciliogenesis in normal and cancer cells although with limited success, especially when concerning the latter. In this study, we evaluated the presence and frequency of primary cilia in breast fibroblasts and in triple-negative breast cancer cells after treatment with cytostatics finding that, in the case of breast fibroblasts, primary cilia were detected at their highest incidence 72 hours after treatment with 120 nM doxorubicin. Further, multiciliated cells were also detected after treatment with 80 nM doxorubicin. On the other hand, treatment with taxol increased the number of ciliated cells only at low concentrations (1.25 and 3.25 nM) and did not induce multiciliation. Interestingly, triple-negative breast cancer cells did not present primary cilia after treatment with either doxorubicin or taxol. This is the first study reporting the presence of multiple primary cilia in breast fibroblasts induced by doxorubicin. However, the null effect of these cytostatics on primary cilia incidence in the evaluated triple negative breast carcinomas cell lines requires further research.

Erratum In

PubMed

See more in PubMed

Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA. HEF1‐dependent Aurora A activation induces disassembly of the primary cilium. Cell. 2007;129:1351‐1363. PubMed PMC

Li A, Saito M, Chuang J‐Z, et al. Ciliary transition zone activation of phosphorylated Tctex‐1 controls ciliary resorption, S‐phase entry and fate of neural progenitors. Nat Cell Biol. 2011;13:402‐411. PubMed PMC

Spalluto C, Wilson DI, Hearn T. Evidence for reciliation of RPE1 cells in late G1 phase, and ciliary localisation of cyclin B1. FEBS Open Bio. 2013;3:334‐340. PubMed PMC

Luesma MJ, Cantarero I, Castiella T, Soriano M, Garcia‐Verdugo JM, Junquera C. Enteric neurons show a primary cilium. J. Cell. Mol. Med. 2013;17:147‐153. PubMed PMC

Malone A, Anderson CT, Tummala P, et al. Primary cilia mediate mechanosensing in bone cells by a calcium‐independent mechanism. Proc. Natl. Acad. Sci. U.S.A. 2007;104:13325‐13330. PubMed PMC

Nigg EA. Origins and consequences of centrosome aberrations in human cancers. Int. J. Cancer. 2006;119:2717‐2723. PubMed

Nigg EA, Čajánek L, Arquint C. The centrosome duplication cycle in health and disease. FEBS Lett. 2014;588:2366‐2372. PubMed

Conroy PC, Saladino C, Dantas TJ, Lalor P, Dockery P, Morrison CG. C‐NAP1 and rootletin restrain DNA damage‐induced centriole splitting and facilitate ciliogenesis. Cell Cycle. 2012;11:3769‐3778. PubMed PMC

Filipová A, Diaz‐Garcia D, Bezrouk A, et al. Ionizing radiation increases primary cilia incidence and induces multiciliation in C2C12 myoblasts: Induction of primary cilia by irradiation. Cell Biol Int. 2015;39:943‐953. PubMed

Lee K, Battini L, Gusella GL. Cilium, centrosome and cell cycle regulation in polycystic kidney disease. Biochim. Biophys. Acta. 2011;1812:1263‐1271. PubMed PMC

Yuan K, Frolova N, Xie YI, et al. Primary cilia are decreased in breast cancer: analysis of a collection of human breast cancer cell lines and tissues. J. Histochem. Cytochem. 2010;58:857‐870. PubMed PMC

Habib JG, O’Shaughnessy JA. The hedgehog pathway in triple‐negative breast cancer. Cancer Med. 2016;5:2989‐3006. PubMed PMC

Dubuc C, Savard M, Bovenzi V, et al. Targeting intracellular B2 receptors using novel cell‐penetrating antagonists to arrest growth and induce apoptosis in human triple‐negative breast cancer. Oncotarget. 2018;9:9885‐9906. PubMed PMC

Hofman J, Skarka A, Havrankova J, Wsol V. Pharmacokinetic interactions of breast cancer chemotherapeutics with human doxorubicin reductases. Biochem Pharmacol. 2015;96:168‐178. PubMed

Sharma N, Kosan ZA, Stallworth JE, Berbari NF, Yoder BK. Soluble levels of cytosolic tubulin regulate ciliary length control. Mol. Biol. Cell. 2011;22:806‐816. PubMed PMC

Bershteyn M, Atwood SX, Woo W‐M, Li M, Oro AE. MIM and cortactin antagonism regulates ciliogenesis and hedgehog signaling. Dev Cell. 2010;19:270‐283. PubMed PMC

Kim J, Lee JE, Heynen‐Genel S, et al. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature. 2010;464:1048‐1051. PubMed PMC

Goranci‐Buzhala G, Gabriel E, Mariappan A, Gopalakrishnan J. Losers of primary cilia gain the benefit of survival. Cancer Discov. 2017;7:1374‐1375. PubMed

Stinchcombe JC, Salio M, Cerundolo V, Pende D, Arico M, Griffiths GM. Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems. BMC Biol. 2011;9:45. PubMed PMC

Dvořák J, Sitorová V, Nikolov HD, et al. Primární řasinky a jejich biologické funkce. Onkologie. 2011;5:234‐238.

Liu A, Wang B, Niswander LA. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development. 2005;132:3103‐3111. PubMed

Gerhardt C, Leu T, Lier JM, Rüther U. The cilia‐regulated proteasome and its role in the development of ciliopathies and cancer. Cilia. 2016;5:14. PubMed PMC

Giannakakou P, Robey R, Fojo T, Blagosklonny MV. Low concentrations of paclitaxel induce cell type‐dependent p53, p21 and G1/G2 arrest instead of mitotic arrest: molecular determinants of paclitaxel‐induced cytotoxicity. Oncogene. 2001;20:3806‐3813. PubMed

Menzl I, Lebeau L, Pandey R, et al. Loss of primary cilia occurs early in breast cancer development. Cilia. 2014;3:7. PubMed PMC

Hassounah NB, Nunez M, Fordyce C, et al. Inhibition of ciliogenesis promotes hedgehog signaling, tumorigenesis, and metastasis in breast cancer. Mol. Cancer Res. 2017;15:1421‐1430. PubMed PMC

Alli E, Yang J‐M, Hait WN. Silencing of stathmin induces tumor‐suppressor function in breast cancer cell lines harboring mutant p53. Oncogene. 2007;26:1003‐1012. PubMed

Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF. Abnormal Centrosome Amplification in the Absence of p53. Science. 1996;271:1744‐1747. PubMed

Nigg EA. Centrosome aberrations: cause or consequence of cancer progression? Nat. Rev. Cancer. 2002;2:815‐825. PubMed

Tutt A, Gabriel A, Bertwistle D, et al. Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification. Curr. Biol. 1999;9:1107‐1110. PubMed

Mahjoub MR, Stearns T. Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling. Curr. Biol. 2012;22:1628‐1634. PubMed PMC

Lancaster MA, Schroth J, Gleeson JG. Subcellular spatial regulation of canonical Wnt signalling at the primary cilium. Nat. Cell Biol. 2011;13:700‐707. PubMed PMC

Plotnikova OV, Pugacheva EN, Golemis EA. Primary cilia and the cell cycle. Methods Cell Biol. 2009;94:137‐160. PubMed PMC

Nobutani K, Shimono Y, Yoshida M, et al. Absence of primary cilia in cell cycle‐arrested human breast cancer cells. Genes Cells. 2014;19:141‐152. PubMed

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...