Haploinsufficiency of SGO1 Results in Deregulated Centrosome Dynamics, Enhanced Chromosomal Instability and Colon Tumorigenesis

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2012 Jan 21

PMID 22262168

Citations 45

Authors

Hiroshi Y Yamada

Yixin Yao

Xiaoxing Wang

Yuting Zhang

Ying Huang

Wei Dai

Chinthalapally V Rao

Affiliations

Soon will be listed here.

Abstract

Chromosome instability (CIN) is found in 85% of colorectal cancers. Defects in mitotic processes are implicated in high CIN and may be critical events in colorectal tumorigenesis. Shugoshin-1 (SGO1) aids in the maintenance of chromosome cohesion and prevents premature chromosome separation and CIN. In addition, integrity of the centrosome may be compromised due to the deficiency of Cohesin and Sgo1 through the disengagement of centrioles. We report here the generation and characterization of SGO1-mutant mice and show that haploinsufficiency of SGO1 leads to enhanced colonic tumorigenesis. Complete disruption of SGO1 results in embryonic lethality, whereas SGO1+/- mice are viable and fertile. Haploinsufficiency of SGO1 results in genomic instability manifested as missegregation of chromosomes and formation of extra centrosomal foci in both murine embryonic fibroblasts and adult bone marrow cells. Enhanced CIN observed in SGO1-deficient mice resulted in an increase in formation of aberrant crypt foci (ACF) and accelerated development of tumors after exposure to azoxymethane (AOM), a colon carcinogen. Together, these results suggest that haploinsufficiency of SGO1 causes enhanced CIN, colonic preneoplastic lesions and tumorigenesis in mice. SGO1 is essential for the suppression of CIN and tumor formation.

Citing Articles

Shugoshin 1 expression in various cancers: a potential target for therapy.

Ankathatti Narayanaswamy I, Kattepur A, Raju K, Perumal V, Ramalingam R, Raavi V Clin Transl Oncol. 2024; .

PMID: 39476301 DOI: 10.1007/s12094-024-03749-1.

Prognosis and biological function of SGOL1 in clear cell renal cell carcinoma: a multiomics analysis.

Yang Z, Jiang Y, Wang L, Yu B, Cai H, Fan J BMC Med Genomics. 2024; 17(1):60.

PMID: 38383432 PMC: 10882763. DOI: 10.1186/s12920-024-01825-7.

Sustained Shugoshin 1 downregulation reduces tumor growth and metastasis in a mouse xenograft tumor model of triple-negative breast cancer.

Jusino S, Rivera-Rivera Y, Chardon-Colon C, Rodriguez-Rodriguez P, Roman-Gonzalez J, Julia-Hernandez V Cell Div. 2023; 18(1):6.

PMID: 37122033 PMC: 10150544. DOI: 10.1186/s13008-023-00088-5.

A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.

Li H, Dong L, Jin M, Li Q, Wang X, Jia M Molecules. 2023; 28(3).

PMID: 36770809 PMC: 9920120. DOI: 10.3390/molecules28031141.

Identification and validation of a potential key gene SGOL1 for poor prognosis in hepatocellular carcinoma based on a bioinformatics approach.

Fei X, Liu S, Liu P, Wang X, Zhu C, Hou J Front Oncol. 2022; 12:1043161.

PMID: 36439418 PMC: 9683735. DOI: 10.3389/fonc.2022.1043161.

References

Deng X, Gao F, Flagg T, Anderson J, May W . Bcl2's flexible loop domain regulates p53 binding and survival. Mol Cell Biol. 2006; 26(12):4421-34. PMC: 1489125. DOI: 10.1128/MCB.01647-05. View

Fenoglio-Preiser C, Noffsinger A . Aberrant crypt foci: A review. Toxicol Pathol. 1999; 27(6):632-42. DOI: 10.1177/019262339902700604. View

Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P . p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003; 11(3):577-90. DOI: 10.1016/s1097-2765(03)00050-9. View

Rao C, Yang Y, Swamy M, Liu T, Fang Y, Mahmood R . Colonic tumorigenesis in BubR1+/-ApcMin/+ compound mutant mice is linked to premature separation of sister chromatids and enhanced genomic instability. Proc Natl Acad Sci U S A. 2005; 102(12):4365-70. PMC: 555497. DOI: 10.1073/pnas.0407822102. View

Dai W, Wang Q, Liu T, Swamy M, Fang Y, Xie S . Slippage of mitotic arrest and enhanced tumor development in mice with BubR1 haploinsufficiency. Cancer Res. 2004; 64(2):440-5. DOI: 10.1158/0008-5472.can-03-3119. View

Wang X, Dai W . Shugoshin, a guardian for sister chromatid segregation. Exp Cell Res. 2005; 310(1):1-9. DOI: 10.1016/j.yexcr.2005.07.018. View

McGuinness B, Hirota T, Kudo N, Peters J, Nasmyth K . Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells. PLoS Biol. 2005; 3(3):e86. PMC: 1054882. DOI: 10.1371/journal.pbio.0030086. View

Duensing A, Duensing S . Guilt by association? p53 and the development of aneuploidy in cancer. Biochem Biophys Res Commun. 2005; 331(3):694-700. DOI: 10.1016/j.bbrc.2005.03.157. View

Kawashima S, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y . Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science. 2009; 327(5962):172-7. DOI: 10.1126/science.1180189. View

10.

Baker D, van Deursen J . Chromosome missegregation causes colon cancer by APC loss of heterozygosity. Cell Cycle. 2010; 9(9):1711-6. PMC: 2963855. DOI: 10.4161/cc.9.9.11314. View

11.

Singh B, Cook K, Vincent L, Hall C, Berry J, Multani A . Cyclooxygenase-2 induces genomic instability, BCL2 expression, doxorubicin resistance, and altered cancer-initiating cell phenotype in MCF7 breast cancer cells. J Surg Res. 2008; 147(2):240-6. DOI: 10.1016/j.jss.2008.02.026. View

12.

Yamada H, Rao C . BRD8 is a potential chemosensitizing target for spindle poisons in colorectal cancer therapy. Int J Oncol. 2009; 35(5):1101-9. DOI: 10.3892/ijo_00000425. View

13.

Wang X, Yang Y, Dai W . Differential subcellular localizations of two human Sgo1 isoforms: implications in regulation of sister chromatid cohesion and microtubule dynamics. Cell Cycle. 2006; 5(6):635-40. View

14.

Van Der Kraak L, Meunier C, Turbide C, Jothy S, Gaboury L, Marcus V . A two-locus system controls susceptibility to colitis-associated colon cancer in mice. Oncotarget. 2011; 1(6):436-446. PMC: 3248117. DOI: 10.18632/oncotarget.177. View

15.

Liu C, Chang S, Narko K, Trifan O, Wu M, Smith E . Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 2001; 276(21):18563-9. DOI: 10.1074/jbc.M010787200. View

16.

Weaver B, Silk A, Montagna C, Verdier-Pinard P, Cleveland D . Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell. 2006; 11(1):25-36. DOI: 10.1016/j.ccr.2006.12.003. View

17.

Rao C, RIVENSON A, Katiwalla M, Kelloff G, Reddy B . Chemopreventive effect of oltipraz during different stages of experimental colon carcinogenesis induced by azoxymethane in male F344 rats. Cancer Res. 1993; 53(11):2502-6. View

18.

Barber T, McManus K, Yuen K, Reis M, Parmigiani G, Shen D . Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc Natl Acad Sci U S A. 2008; 105(9):3443-8. PMC: 2265152. DOI: 10.1073/pnas.0712384105. View

19.

Ganem N, Godinho S, Pellman D . A mechanism linking extra centrosomes to chromosomal instability. Nature. 2009; 460(7252):278-82. PMC: 2743290. DOI: 10.1038/nature08136. View

20.

Rostom A, Dube C, Lewin G, Tsertsvadze A, Barrowman N, Code C . Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med. 2007; 146(5):376-89. DOI: 10.7326/0003-4819-146-5-200703060-00010. View