XIAP Facilitates Breast and Colon Carcinoma Growth Via Promotion of P62 Depletion Through Ubiquitination-dependent Proteasomal Degradation

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2018 Oct 3

PMID 30275562

Citations 19

Authors

Xing Huang

Xiao-Nan Wang

Xiao-Dong Yuan

Wen-Yong Wu

Peter E Lobie

Zhengsheng Wu

Affiliations

Soon will be listed here.

Abstract

X-linked inhibitor of apoptosis protein (XIAP) possesses a critical role in promotion of cell survival and maintenance of cellular homeostasis. In cancer, elevated XIAP expression has been associated with malignancy, poor prognosis, and treatment resistance. However, the underlying mechanisms of these effects remain unclear. XIAP has previously been proposed to promote tumor growth through suppression of autophagy. In this study, we examined the expression of XIAP and p62, two critical mediators of autophagy, in breast and colon cancer. We observed a negative correlation between XIAP and p62 expression in normal and cancer tissues of breast and colon, and that the ratio of XIAP and p62 expression determines the cancer phenotype. In vitro, we observed that XIAP interacted with p62 and also that XIAP depletion resulted in increased expression of p62. XIAP functioned as an ubiquitination E3 ligase towards p62 and suppressed p62 expression through ubiquitin-proteasomal degradation. Furthermore, XIAP enhanced cancer cell proliferation, viability, and colony formation in vitro via suppression of p62. In addition, we demonstrated that XIAP-enhanced tumor growth is dependent on depletion of p62 in vivo. Herein, we have therefore delineated a novel mechanism by which XIAP contributes to development and progression of breast and colon carcinoma.

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References

Holcik M, Korneluk R . XIAP, the guardian angel. Nat Rev Mol Cell Biol. 2001; 2(7):550-6. DOI: 10.1038/35080103. View

Holcik M, Gibson H, Korneluk R . XIAP: apoptotic brake and promising therapeutic target. Apoptosis. 2001; 6(4):253-61. DOI: 10.1023/a:1011379307472. View

Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A . Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003; 112(12):1809-20. PMC: 297002. DOI: 10.1172/JCI20039. View

Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh B . Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol. 2006; 8(7):688-99. DOI: 10.1038/ncb1426. View

Eckelman B, Salvesen G, Scott F . Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep. 2006; 7(10):988-94. PMC: 1618369. DOI: 10.1038/sj.embor.7400795. View

Hunter A, LaCasse E, Korneluk R . The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis. 2007; 12(9):1543-68. DOI: 10.1007/s10495-007-0087-3. View

Takahashi Y, Coppola D, Matsushita N, Cualing H, Sun M, Sato Y . Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007; 9(10):1142-51. PMC: 2254521. DOI: 10.1038/ncb1634. View

Duran A, Linares J, Galvez A, Wikenheiser K, Flores J, Diaz-Meco M . The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell. 2008; 13(4):343-54. DOI: 10.1016/j.ccr.2008.02.001. View

Eskelinen E, Saftig P . Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta. 2008; 1793(4):664-73. DOI: 10.1016/j.bbamcr.2008.07.014. View

10.

LaCasse E, Mahoney D, Cheung H, Plenchette S, Baird S, Korneluk R . IAP-targeted therapies for cancer. Oncogene. 2008; 27(48):6252-75. DOI: 10.1038/onc.2008.302. View

11.

Morselli E, Galluzzi L, Kepp O, Vicencio J, Criollo A, Maiuri M . Anti- and pro-tumor functions of autophagy. Biochim Biophys Acta. 2009; 1793(9):1524-32. DOI: 10.1016/j.bbamcr.2009.01.006. View

12.

Moscat J, Diaz-Meco M . p62 at the crossroads of autophagy, apoptosis, and cancer. Cell. 2009; 137(6):1001-4. PMC: 3971861. DOI: 10.1016/j.cell.2009.05.023. View

13.

Mathew R, Karp C, Beaudoin B, Vuong N, Chen G, Chen H . Autophagy suppresses tumorigenesis through elimination of p62. Cell. 2009; 137(6):1062-75. PMC: 2802318. DOI: 10.1016/j.cell.2009.03.048. View

14.

Pandey V, Qian P, Kang J, Perry J, Mitchell M, Yin Z . Artemin stimulates oncogenicity and invasiveness of human endometrial carcinoma cells. Endocrinology. 2010; 151(3):909-20. DOI: 10.1210/en.2009-0979. View

15.

Kong D, Georgescu S, Cano C, Aronovitz M, Iovanna J, Patten R . Deficiency of the transcriptional regulator p8 results in increased autophagy and apoptosis, and causes impaired heart function. Mol Biol Cell. 2010; 21(8):1335-49. PMC: 2854092. DOI: 10.1091/mbc.e09-09-0818. View

16.

Gao C, Cao W, Bao L, Zuo W, Xie G, Cai T . Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation. Nat Cell Biol. 2010; 12(8):781-90. DOI: 10.1038/ncb2082. View

17.

Hung T, Chen S, Li M, Yeh Y, Hsieh T . Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation. PLoS One. 2010; 5(8):e12202. PMC: 2922378. DOI: 10.1371/journal.pone.0012202. View

18.

Ichimura Y, Komatsu M . Selective degradation of p62 by autophagy. Semin Immunopathol. 2010; 32(4):431-6. DOI: 10.1007/s00281-010-0220-1. View

19.

Linares J, Amanchy R, Greis K, Diaz-Meco M, Moscat J . Phosphorylation of p62 by cdk1 controls the timely transit of cells through mitosis and tumor cell proliferation. Mol Cell Biol. 2010; 31(1):105-17. PMC: 3019844. DOI: 10.1128/MCB.00620-10. View

20.

Lee H, Shin D, Yuk J, Shi G, Choi D, Lee S . Autophagy negatively regulates keratinocyte inflammatory responses via scaffolding protein p62/SQSTM1. J Immunol. 2010; 186(2):1248-58. DOI: 10.4049/jimmunol.1001954. View