The Role of YWHAZ in Cancer: A Maze of Opportunities and Challenges

Overview

Journal J Cancer

Specialty Oncology

Date 2020 Mar 5

PMID 32127952

Citations 52

Authors

Yun Gan

Feng Ye

Xing-Xing He

Affiliations

Soon will be listed here.

Abstract

YWHAZ (also named 14-3-3ζ) is a central hub protein for many signal transduction pathways and plays a significant role in tumor progression. Accumulating evidences have demonstrated that is frequently up-regulated in multiple types of cancers and acts as an oncogene in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration, and invasion. Moreover, was reported to be regulated by microRNAs (miRNAs) or long non-coding RNAs and exerted its malignant functions by targeting downstream molecules like protein kinase, apoptosis proteins, and metastasis-related molecules. Additionally, YWHAZ may be a potential biomarker of diagnosis, prognosis and chemoresistance in several cancers. Targeting by siRNA, shRNA or miRNA was reported to have great help in suppressing malignant properties of cancer cells. In this review, we perform literature and bioinformatics analysis to reveal the oncogenic role and molecular mechanism of YWHAZ in cancer, and discuss the potential clinical applications of YWHAZ concerning diagnosis, prognosis, and therapy in malignant tumors.

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References

Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y . Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med. 2010; 16(2):214-8. PMC: 2826790. DOI: 10.1038/nm.2090. View

Ji N, Wang Y, Bao G, Yan J, Ji S . LncRNA SNHG14 promotes the progression of cervical cancer by regulating miR-206/YWHAZ. Pathol Res Pract. 2019; 215(4):668-675. DOI: 10.1016/j.prp.2018.12.026. View

Bergamaschi A, Madak-Erdogan Z, Kim Y, Choi Y, Lu H, Katzenellenbogen B . The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells. Breast Cancer Res. 2014; 16(5):436. PMC: 4303117. DOI: 10.1186/s13058-014-0436-4. View

Maxwell S, Li Z, Jaya D, Ballard S, Ferrell J, Fu H . 14-3-3zeta mediates resistance of diffuse large B cell lymphoma to an anthracycline-based chemotherapeutic regimen. J Biol Chem. 2009; 284(33):22379-22389. PMC: 2755960. DOI: 10.1074/jbc.M109.022418. View

Lin C, Wu Z, Lin X, Yu C, Shi T, Zeng Y . Knockdown of FLOT1 impairs cell proliferation and tumorigenicity in breast cancer through upregulation of FOXO3a. Clin Cancer Res. 2011; 17(10):3089-99. DOI: 10.1158/1078-0432.CCR-10-3068. View

Rehman S, Li S, Wyszomierski S, Wang Q, Li P, Sahin O . 14-3-3ζ orchestrates mammary tumor onset and progression via miR-221-mediated cell proliferation. Cancer Res. 2013; 74(1):363-373. PMC: 3947305. DOI: 10.1158/0008-5472.CAN-13-2016. View

Jiang X, Wu J, Zhang Y, Wang S, Yu X, Li R . MiR-613 functions as tumor suppressor in hepatocellular carcinoma by targeting YWHAZ. Gene. 2018; 659:168-174. DOI: 10.1016/j.gene.2018.03.036. View

Sheng N, Yan L, Wu K, You W, Gong J, Hu L . TRIP13 promotes tumor growth and is associated with poor prognosis in colorectal cancer. Cell Death Dis. 2018; 9(3):402. PMC: 5852242. DOI: 10.1038/s41419-018-0434-z. View

Tang Y, Liu S, Li N, Guo W, Shi J, Yu H . 14-3-3ζ promotes hepatocellular carcinoma venous metastasis by modulating hypoxia-inducible factor-1α. Oncotarget. 2016; 7(13):15854-67. PMC: 4941282. DOI: 10.18632/oncotarget.7493. View

10.

Qin J, Wang S, Wang P, Wang X, Ye H, Song C . Autoantibody against 14-3-3 zeta: a serological marker in detection of gastric cancer. J Cancer Res Clin Oncol. 2019; 145(5):1253-1262. DOI: 10.1007/s00432-019-02884-5. View

11.

Murata T, Takayama K, Urano T, Fujimura T, Ashikari D, Obinata D . 14-3-3ζ, a novel androgen-responsive gene, is upregulated in prostate cancer and promotes prostate cancer cell proliferation and survival. Clin Cancer Res. 2012; 18(20):5617-27. DOI: 10.1158/1078-0432.CCR-12-0281. View

12.

Mitri Z, Constantine T, ORegan R . The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in Therapy. Chemother Res Pract. 2013; 2012:743193. PMC: 3539433. DOI: 10.1155/2012/743193. View

13.

Ruenauver K, Menon R, Svensson M, Carlsson J, Vogel W, Andren O . Prognostic significance of YWHAZ expression in localized prostate cancer. Prostate Cancer Prostatic Dis. 2014; 17(4):310-4. DOI: 10.1038/pcan.2014.32. View

14.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

15.

Guo F, Jiao D, Sui G, Sun L, Gao Y, Fu Q . Anticancer effect of YWHAZ silencing via inducing apoptosis and autophagy in gastric cancer cells. Neoplasma. 2018; 65(5):693-700. DOI: 10.4149/neo_2018_170922N603. View

16.

Chen C, Chuang S, Yang M, Liao J, Yu S, Chen J . A novel function of YWHAZ/β-catenin axis in promoting epithelial-mesenchymal transition and lung cancer metastasis. Mol Cancer Res. 2012; 10(10):1319-31. DOI: 10.1158/1541-7786.MCR-12-0189. View

17.

Bergamaschi A, Frasor J, Borgen K, Stanculescu A, Johnson P, Rowland K . 14-3-3ζ as a predictor of early time to recurrence and distant metastasis in hormone receptor-positive and -negative breast cancers. Breast Cancer Res Treat. 2012; 137(3):689-96. PMC: 3632437. DOI: 10.1007/s10549-012-2390-0. View

18.

Stark G, Taylor W . Analyzing the G2/M checkpoint. Methods Mol Biol. 2004; 280:51-82. DOI: 10.1385/1-59259-788-2:051. View

19.

Sunayama J, Sato A, Matsuda K, Tachibana K, Watanabe E, Seino S . FoxO3a functions as a key integrator of cellular signals that control glioblastoma stem-like cell differentiation and tumorigenicity. Stem Cells. 2011; 29(9):1327-37. DOI: 10.1002/stem.696. View

20.

Liang S, Shen G, Liu Q, Xu Y, Zhou L, Xiao S . Isoform-specific expression and characterization of 14-3-3 proteins in human glioma tissues discovered by stable isotope labeling with amino acids in cell culture-based proteomic analysis. Proteomics Clin Appl. 2010; 3(6):743-53. DOI: 10.1002/prca.200800198. View