Bestrophin-4 Relays HES4 and Interacts with TWIST1 to Suppress Epithelial-to-mesenchymal Transition in Colorectal Cancer Cells

Overview

Journal Elife

Specialty Biology

Date 2024 Dec 19

PMID 39699952

Authors

Zijing Wang

Bihan Xia

Shaochong Qi

Xian Zhang

Xiaoshuang Zhang

Yan Li

Huimin Wang

Miao Zhang

Ziyi Zhao

David Kerr

Li Yang

Shijie Cai

Jilin Yang

Affiliations

Soon will be listed here.

Abstract

Bestrophin isoform 4 () is a newly identified subtype of the calcium-activated chloride channel family. Analysis of colonic epithelial cell diversity by single-cell RNA-sequencing has revealed the existence of a cluster of + mature colonocytes in humans. However, if the role of is involved in regulating tumour progression remains largely unknown. In this study, we demonstrate that overexpression attenuates cell proliferation, colony formation, and mobility in colorectal cancer (CRC) in vitro, and impedes the tumour growth and the liver metastasis in vivo. BEST4 is co-expressed with hairy/enhancer of split 4 () in the nucleus of cells, and HES4 signals by interacting with the upstream region of the promoter. is epistatic to and downregulates TWIST1, thereby inhibiting epithelial-to-mesenchymal transition (EMT) in CRC. Conversely, knockout of BEST4 using CRISPR/Cas9 in CRC cells revitalises tumour growth and induces EMT. Furthermore, the low level of the mRNA is correlated with advanced and the worse prognosis, suggesting its potential role involving CRC progression.

References

Marmorstein A, Cross H, Peachey N . Functional roles of bestrophins in ocular epithelia. Prog Retin Eye Res. 2009; 28(3):206-26. PMC: 2740978. DOI: 10.1016/j.preteyeres.2009.04.004. View

Zhu D, Chen X, Zhang W, Wang J, Ouyang M, Zhong Q . Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance. Am J Cancer Res. 2015; 5(6):2000-11. PMC: 4529619. View

Yusup A, Huji B, Fang C, Wang F, Dadihan T, Wang H . Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis. World J Gastroenterol. 2017; 23(1):110-120. PMC: 5221274. DOI: 10.3748/wjg.v23.i1.110. View

Nagai T, Arao T, Nishio K, Matsumoto K, Hagiwara S, Sakurai T . Impact of Tight Junction Protein ZO-1 and TWIST Expression on Postoperative Survival of Patients with Hepatocellular Carcinoma. Dig Dis. 2016; 34(6):702-707. DOI: 10.1159/000448860. View

Katoh M, Katoh M . Identification and characterization of human HES2, HES3, and HES5 genes in silico. Int J Oncol. 2004; 25(2):529-34. View

Yuan R, Ke J, Sun L, He Z, Zou Y, He X . HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer. Clin Exp Metastasis. 2015; 32(2):169-79. DOI: 10.1007/s10585-015-9700-y. View

Tsunenari T, Sun H, Williams J, Cahill H, Smallwood P, Yau K . Structure-function analysis of the bestrophin family of anion channels. J Biol Chem. 2003; 278(42):41114-25. PMC: 2885917. DOI: 10.1074/jbc.M306150200. View

Liu Y, Zhang H, Huang D, Qi J, Xu J, Gao H . Characterization of the effects of Cl⁻ channel modulators on TMEM16A and bestrophin-1 Ca²⁺ activated Cl⁻ channels. Pflugers Arch. 2014; 467(7):1417-1430. DOI: 10.1007/s00424-014-1572-5. View

Miller A, Vaisey G, Long S . Molecular mechanisms of gating in the calcium-activated chloride channel bestrophin. Elife. 2019; 8. PMC: 6342527. DOI: 10.7554/eLife.43231. View

10.

Uwada J, Yazawa T, Nakazawa H, Mikami D, Krug S, Fromm M . Store-operated calcium entry (SOCE) contributes to phosphorylation of p38 MAPK and suppression of TNF-α signalling in the intestinal epithelial cells. Cell Signal. 2019; 63:109358. DOI: 10.1016/j.cellsig.2019.109358. View

11.

Wang Z, Kawaguchi K, Honda M, Hashimoto S, Shirasaki T, Okada H . Notch signaling facilitates hepatitis B virus covalently closed circular DNA transcription via cAMP response element-binding protein with E3 ubiquitin ligase-modulation. Sci Rep. 2019; 9(1):1621. PMC: 6367350. DOI: 10.1038/s41598-018-38139-5. View

12.

Fagerberg L, Hallstrom B, Oksvold P, Kampf C, Djureinovic D, Odeberg J . Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2013; 13(2):397-406. PMC: 3916642. DOI: 10.1074/mcp.M113.035600. View

13.

Acloque H, Adams M, Fishwick K, Bronner-Fraser M, Nieto M . Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009; 119(6):1438-49. PMC: 2689100. DOI: 10.1172/JCI38019. View

14.

Meng J, Chen S, Han J, Qian B, Wang X, Zhong W . Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma. Cancer Res. 2018; 78(15):4150-4162. DOI: 10.1158/0008-5472.CAN-17-3009. View

15.

Huang F, Wong X, Jan L . International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels. Pharmacol Rev. 2011; 64(1):1-15. PMC: 3250081. DOI: 10.1124/pr.111.005009. View

16.

Sanders K, Zhu M, Britton F, Koh S, Ward S . Anoctamins and gastrointestinal smooth muscle excitability. Exp Physiol. 2011; 97(2):200-6. PMC: 3272164. DOI: 10.1113/expphysiol.2011.058248. View

17.

Pastushenko I, Blanpain C . EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol. 2018; 29(3):212-226. DOI: 10.1016/j.tcb.2018.12.001. View

18.

Ito G, Okamoto R, Murano T, Shimizu H, Fujii S, Nakata T . Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells. PLoS One. 2013; 8(11):e79693. PMC: 3818177. DOI: 10.1371/journal.pone.0079693. View

19.

Milenkovic V, Langmann T, Schreiber R, Kunzelmann K, Weber B . Molecular evolution and functional divergence of the bestrophin protein family. BMC Evol Biol. 2008; 8:72. PMC: 2292144. DOI: 10.1186/1471-2148-8-72. View

20.

Zhang N, Ng A, Cai S, Li Q, Yang L, Kerr D . Novel therapeutic strategies: targeting epithelial-mesenchymal transition in colorectal cancer. Lancet Oncol. 2021; 22(8):e358-e368. DOI: 10.1016/S1470-2045(21)00343-0. View