Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Jul 12

PMID 28696368

Citations 31

Authors

Svetlana Bortnik

Sharon M Gorski

Affiliations

Soon will be listed here.

Abstract

Autophagy, a lysosome-mediated intracellular degradation and recycling pathway, plays multiple context-dependent roles in tumorigenesis and treatment resistance. Encouraging results from various preclinical studies have led to the initiation of numerous clinical trials with the intention of targeting autophagy in various cancers. Accumulating knowledge of the particular mechanisms and players involved in different steps of autophagy regulation led to the ongoing discovery of small molecule inhibitors designed to disrupt this highly orchestrated process. However, the development of validated autophagy-related biomarkers, essential for rational selection of patients entering clinical trials involving autophagy inhibitors, is lagging behind. One possible source of biomarkers for this purpose is the autophagy machinery itself. In this review, we address the recent trends, challenges and advances in the assessment of the biomarker potential of clinically relevant autophagy proteins in human cancers.

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References

Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F . A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014; 10(12):1013-9. DOI: 10.1038/nchembio.1681. View

He Y, Zhao X, Subahan N, Fan L, Gao J, Chen H . The prognostic value of autophagy-related markers beclin-1 and microtubule-associated protein light chain 3B in cancers: a systematic review and meta-analysis. Tumour Biol. 2014; 35(8):7317-26. DOI: 10.1007/s13277-014-2060-4. View

Zhao H, Yang M, Zhao J, Wang J, Zhang Y, Zhang Q . High expression of LC3B is associated with progression and poor outcome in triple-negative breast cancer. Med Oncol. 2013; 30(1):475. DOI: 10.1007/s12032-013-0475-1. View

Masuda G, Yashiro M, Kitayama K, Miki Y, Kasashima H, Kinoshita H . Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer. Anticancer Res. 2016; 36(1):129-36. View

Tang J, Deng R, Luo R, Shen G, Cai M, Du Z . Low expression of ULK1 is associated with operable breast cancer progression and is an adverse prognostic marker of survival for patients. Breast Cancer Res Treat. 2012; 134(2):549-60. DOI: 10.1007/s10549-012-2080-y. View

Zhong Z, Sanchez-Lopez E, Karin M . Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment. Cell. 2016; 166(2):288-298. PMC: 4947210. DOI: 10.1016/j.cell.2016.05.051. View

Xu H, Yu H, Zhang X, Shen X, Zhang K, Sheng H . UNC51-like kinase 1 as a potential prognostic biomarker for hepatocellular carcinoma. Int J Clin Exp Pathol. 2013; 6(4):711-7. PMC: 3606861. View

Jiang L, Duan B, Huang J, Jiao X, Zhu X, Sheng H . Association of the expression of unc-51-Like kinase 1 with lymph node metastasis and survival in patients with esophageal squamous cell carcinoma. Int J Clin Exp Med. 2014; 7(5):1349-54. PMC: 4073755. View

Nguyen T, Padman B, Usher J, Oorschot V, Ramm G, Lazarou M . Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. J Cell Biol. 2016; 215(6):857-874. PMC: 5166504. DOI: 10.1083/jcb.201607039. View

10.

Wu S, Sun C, Tian D, Li Y, Gao X, He S . Expression and clinical significances of Beclin1, LC3 and mTOR in colorectal cancer. Int J Clin Exp Pathol. 2015; 8(4):3882-91. PMC: 4466959. View

11.

Eissa S, Matboli M, Awad N, Kotb Y . Identification and validation of a novel autophagy gene expression signature for human bladder cancer patients. Tumour Biol. 2017; 39(4):1010428317698360. DOI: 10.1177/1010428317698360. View

12.

Italiano A . Prognostic or predictive? It's time to get back to definitions!. J Clin Oncol. 2011; 29(35):4718. DOI: 10.1200/JCO.2011.38.3729. View

13.

Kim M, Song S, Lee J, Yoo N, Lee S . Expressional and mutational analyses of ATG5 gene in prostate cancers. APMIS. 2011; 119(11):802-7. DOI: 10.1111/j.1600-0463.2011.02812.x. View

14.

Mehta S, Shelling A, Muthukaruppan A, Lasham A, Blenkiron C, Laking G . Predictive and prognostic molecular markers for cancer medicine. Ther Adv Med Oncol. 2011; 2(2):125-48. PMC: 3126011. DOI: 10.1177/1758834009360519. View

15.

Carvajal-Hausdorf D, Schalper K, Neumeister V, Rimm D . Quantitative measurement of cancer tissue biomarkers in the lab and in the clinic. Lab Invest. 2014; 95(4):385-96. PMC: 4383674. DOI: 10.1038/labinvest.2014.157. View

16.

Spowart J, Townsend K, Huwait H, Eshragh S, West N, Ries J . The autophagy protein LC3A correlates with hypoxia and is a prognostic marker of patient survival in clear cell ovarian cancer. J Pathol. 2012; 228(4):437-47. DOI: 10.1002/path.4090. View

17.

Rolland P, Madjd Z, Durrant L, Ellis I, Layfield R, Spendlove I . The ubiquitin-binding protein p62 is expressed in breast cancers showing features of aggressive disease. Endocr Relat Cancer. 2007; 14(1):73-80. DOI: 10.1677/erc.1.01312. View

18.

Bago R, Malik N, Munson M, Prescott A, Davies P, Sommer E . Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. Biochem J. 2014; 463(3):413-27. PMC: 4209782. DOI: 10.1042/BJ20140889. View

19.

An C, Kim M, Yoo N, Park S, Lee S . Mutational and expressional analyses of ATG5, an autophagy-related gene, in gastrointestinal cancers. Pathol Res Pract. 2011; 207(7):433-7. DOI: 10.1016/j.prp.2011.05.002. View

20.

Lin M, Hurley J . Structure and function of the ULK1 complex in autophagy. Curr Opin Cell Biol. 2016; 39:61-8. PMC: 4828305. DOI: 10.1016/j.ceb.2016.02.010. View