The Biological Roles of ZKSCAN3 (ZNF306) in the Hallmarks of Cancer: From Mechanisms to Therapeutics

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Nov 9

PMID 39519085

Authors

Wenfang Li

Han Zhang

Jianxiong Xu

Ayitila Maimaitijiang

Zhengding Su

Zhongxiong Fan

Jinyao Li

Affiliations

Soon will be listed here.

Abstract

ZKSCAN3 (also known as ZNF306) plays a pivotal role in the regulation of various cellular processes that are fundamental to the development of cancer. It has been widely acknowledged as a key contributor to cancer progression, with its overexpression consistently reported in a broad spectrum of malignancies. Importantly, clinical studies have demonstrated a significant association between elevated ZKSCAN3 levels and adverse prognosis, as well as resistance to therapeutic drugs. Specifically, ZKSCAN3 promotes tumor progression by enhancing multiple hallmark features of cancer and promoting the acquisition of cancer-specific phenotypes. These effects manifest as increased tumor cell proliferation, invasion, and metastasis, accompanied by inhibiting tumor cell apoptosis and modulating autophagy. Consequently, ZKSCAN3 emerges as a promising prognostic marker, and targeting its inhibition represents a potential strategy for anti-tumor therapy. In this review, we provide an updated perspective on the role of ZKSCAN3 in governing tumor characteristics and the underlying molecular mechanisms. Furthermore, we underscore the clinical relevance of ZKSCAN3 and its potential implications for tumor prognosis and therapeutic strategies.

References

Lee S, Cho Y, Kim J, Park J . ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer. Int J Mol Sci. 2018; 19(10). PMC: 6213532. DOI: 10.3390/ijms19102859. View

Zhang X, Jing Y, Qin Y, Hunsucker S, Meng H, Sui J . The zinc finger transcription factor ZKSCAN3 promotes prostate cancer cell migration. Int J Biochem Cell Biol. 2012; 44(7):1166-73. PMC: 3358443. DOI: 10.1016/j.biocel.2012.04.005. View

Debnath J, Gammoh N, Ryan K . Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol. 2023; 24(8):560-575. PMC: 9980873. DOI: 10.1038/s41580-023-00585-z. View

Charrier A, Ockunzzi J, Main L, Ghanta S, Buchner D . Molecular regulation of PPARγ/RXRα signaling by the novel cofactor ZFP407. PLoS One. 2024; 19(5):e0294003. PMC: 11115250. DOI: 10.1371/journal.pone.0294003. View

Eldeeb M, Thomas R, Ragheb M, Fallahi A, Fon E . Mitochondrial quality control in health and in Parkinson's disease. Physiol Rev. 2022; 102(4):1721-1755. DOI: 10.1152/physrev.00041.2021. View

Li W, Alfason L, Huang C, Tang Y, Qiu L, Miyagishi M . p52-ZER6: a determinant of tumor cell sensitivity to MDM2-p53 binding inhibitors. Acta Pharmacol Sin. 2022; 44(3):647-660. PMC: 9958181. DOI: 10.1038/s41401-022-00973-9. View

Jacobs E, Anderson R, Stevens V, Newton C, Gansler T, Gapstur S . Vasectomy and Prostate Cancer Incidence and Mortality in a Large US Cohort. J Clin Oncol. 2016; 34(32):3880-3885. PMC: 6366294. DOI: 10.1200/JCO.2015.66.2361. View

Li X, Wen J, Feng Z, Wu Y, Li D, Liang S . Effect of Lacking ZKSCAN3 on Autophagy, Lysosomal Biogenesis and Senescence. Int J Mol Sci. 2023; 24(9). PMC: 10178544. DOI: 10.3390/ijms24097786. View

Liu Z, Li X, Li X, Li Z, Chen H, Gong S . The kidney-expressed transcription factor ZKSCAN3 is dispensable for autophagy transcriptional regulation and AKI progression in mouse. Mutat Res. 2022; 825:111790. DOI: 10.1016/j.mrfmmm.2022.111790. View

10.

Mucci L, Wilson K, Preston M, Giovannucci E . Is Vasectomy a Cause of Prostate Cancer?. J Natl Cancer Inst. 2019; 112(1):5-6. DOI: 10.1093/jnci/djz102. View

11.

Vitale I, Pietrocola F, Guilbaud E, Aaronson S, Abrams J, Adam D . Apoptotic cell death in disease-Current understanding of the NCCD 2023. Cell Death Differ. 2023; 30(5):1097-1154. PMC: 10130819. DOI: 10.1038/s41418-023-01153-w. View

12.

Cui J, Bai X, Chen X . Autophagy and Acute Kidney Injury. Adv Exp Med Biol. 2020; 1207:469-480. DOI: 10.1007/978-981-15-4272-5_34. View

13.

Nonoyama K, Matsuo Y, Sugita S, Eguchi Y, Denda Y, Murase H . Expression of ZKSCAN3 protein suppresses proliferation, migration, and invasion of pancreatic cancer through autophagy. Cancer Sci. 2024; 115(6):1964-1978. PMC: 11145104. DOI: 10.1111/cas.16173. View

14.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

15.

Li Y, Xu M, Ding X, Yan C, Song Z, Chen L . Protein kinase C controls lysosome biogenesis independently of mTORC1. Nat Cell Biol. 2016; 18(10):1065-77. DOI: 10.1038/ncb3407. View

16.

Settembre C, Perera R . Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology. Nat Rev Mol Cell Biol. 2023; 25(3):223-245. DOI: 10.1038/s41580-023-00676-x. View

17.

Carneiro B, El-Deiry W . Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. 2020; 17(7):395-417. PMC: 8211386. DOI: 10.1038/s41571-020-0341-y. View

18.

Chi Y, Xu H, Wang F, Chen X, Shan Z, Sun Y . ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion. Biochem Biophys Res Commun. 2018; 503(4):2583-2589. DOI: 10.1016/j.bbrc.2018.07.019. View

19.

Li J, Hao N, Han J, Zhang M, Li X, Yang N . ZKSCAN3 drives tumor metastasis via integrin β4/FAK/AKT mediated epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Cell Int. 2020; 20:216. PMC: 7275473. DOI: 10.1186/s12935-020-01307-7. View

20.

Wu X, Ren Y, Wen Y, Lu S, Li H, Yu H . Deacetylation of ZKSCAN3 by SIRT1 induces autophagy and protects SN4741 cells against MPP-induced oxidative stress. Free Radic Biol Med. 2022; 181:82-97. DOI: 10.1016/j.freeradbiomed.2022.02.001. View