Cancer Letters 483 (2020) 75–86 the possibility that myosin-9 promotes cancer metastasis through

 W. Zhou, et al. Cancer Letters 483 (2020) 75–86 the possibility that myosin-9 promotes cancer metastasis through [5] S.M. Kolk, R.J. Pasterkamp, MICALflavoprotein monooxygenases: structure, func- tion and role in semaphorin signaling, Adv. Exp. Med. Biol. 600 (2007) 38–51. MICAL2 in LUADs. First, the redox-regulation of myosin-9 results in [6] Y. Cai, J. Lu, F. Tang, Overexpression of MICAL2, a novel tumor-promoting factor, microfilamentremodelingandalteredcellularmotility[50].Giventhat accelerates tumor progression through regulating cell proliferation and EMT, J. MICAL2isaredoxenzyme[9,51]andthatmyosin-9wasshowntobind Canc. 9 (2018) 521–527. [7] J. Fischer, T. Weide, A. Barnekow, The MICAL proteins and rab1: a possible link to MICAL2 (Fig. 4), further study could focus on whether MICAL2 can the cytoskeleton? Biochem Temozolomide. Biophys. Res. Commun Hexa His tag peptide. 328 (2005) 415–423. redox myosin-9 regulating microfilament depolymerization. Secondly, [8] B.C.Lee,Z.Péterfi,F.W.Hoffmann,R.E.Moore,A.Kaya,A.Avanesov,etal.,MsrB1 myosin filament organization is regulated by small Rho GTPases [52] and MICALs regulate assembly and macrophage function via reversible ste- reoselective methionine oxidation, Mol. Cell. 51 (2013) 397–404. and the activation of Rac1 (a member of the Rho family) is affected by [9] L.T. Alto, J.R. Terman, MICALs, Curr. Biol. 28 (2018) R538–R541. MICAL2 [14]; thus, MICAL2 can also regulate myosin-9 through Rac1. [10] S. Frémont, G. Romet-Lemonne, A. Houdusse, 

 

A. Echard, Emerging roles of MICAL Thirdly, myosin-9 is reportedly involved in lamellipodia extension family proteins – from actin oxidation to membrane trafficking during cytokinesis, J. Cell Sci. 130 (2017) 1509–1517. based on its assembly regulation or as an ABP (actin-binding protein) [11] S.S. Giridharan, J.L. Rohn, N. Naslavsky, S. Caplan, Differential regulation of actin regulating the actin network [53]. Given that MICAL2 can directly microfilaments by human MICAL proteins, J. Cell Sci. 125 (2012) 614–624. depolymerize F-actin [19] and improve the binding of cofilin (an ABP) [12] S. Ashida, M. Furihata, T. Katagiri, K. Tamura, Y. Anazawa, H. Yoshioka, et al., Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), in- tofilaments [54], it is possible that MICAL2 also regulates F-actin and creaseswithhighGleasonscoreandprostatecancerprogression,Clin.Canc.Res.12 promotes lamellipodia formation through myosin-9. Altogether, the (2006) 2767–2773. regulation between MICAL2 and myosin-9 is mutual, variable, and acts [13] S. Mariotti, I. Barravecchia, C. Vindigni, A. Pucci, M. Balsamo, R. Libro, et al., instereo,leadingtocellmigrationandtumormetastasis.Consequently, MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transitioninvolvedincancergrowthandinvasion,Oncotarget7(2016)1808–1825. future studies should explore the synergistic anti-tumor activity that [14] Y. Wang, W. Deng, Y. Zhang, S. Sun, S. Zhao, Y. Chen, et al., MICAL2 promotes ensues when pairing MICAL2 inhibitors with myosin-9 inhibitors. breast cancer cell migration by maintaining epidermal growth factor receptor In summary, our research demonstrates that subcellular MICAL2 (EGFR) stability and EGFR/P38 signalling activation, Acta Physiol. 222 (2018) e12920. expression levels are significantly correlated with prognosis in LUAD [15] J.Lu,Y.Li,Y.Wu,S.Zhou,C.Duan,Z.Dong,etal.,MICAL2mediatesp53ubiquitin patients and play an important role in LUAD cell proliferation and in- degradationthroughoxidatingp53methionine40and160andpromotescolorectal vasion.MICAL2isanuclear-cytoplasmicshuttlingproteininLUADcells cancer malignance cck-8 price, Theranostics 8 (2018) 5289–5306. [16] M.R. Lundquist, A.J. Storaska, T. Liu, S.D. Larsen, T. Evans, R.R. Neubig, et al., which relies on its C-terminal fragment as well as myosin-9. Applying Redox modification of nuclear actin by MICAL-2 regulates SRF signaling, Cell 156 LMB, ML7, or si-myosin-9 or deleting the C-terminal end of MICAL2 (2014) 563–576. inhibits its nuclear export as well as its carcinogenic effects. This study [17] Y. Cai, J. Lu, F. Tang, Overexpression of MICAL2, a novel tumor-promoting factor, accelerates tumor progression through regulating cell proliferation and EMT, J. contributes to our ever-increasing understanding of the subcellular Canc. 9 (2018) 521–527. distribution and carcinogenicity of MICAL2 and suggests that MICAL2 [18] S. Mariotti, I. Barravecchia, C. Vindigni, A. Pucci, M. Balsamo, R. Libro, et al., is a promising cancer marker candidate and therapeutic target for MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial LUAD. transitioninvolvedincancergrowthandinvasion,Oncot###http://www.glpbio.com/simage/GA11366-H-D-Leu-Thr-Arg-pNA-acetate-salt-2.png####arget7(2016)1808–1825. [19] S.S.P. Giridharan, J.L. Rohn, N. Naslavsky, S. Caplan, Differential regulation of actin microfilaments by human MICAL proteins, J. Cell Sci. 125 (2012) 614–624. Funding sources [20] I. Barravecchia, S. Mariotti, A. Pucci, F. Scebba, C. De Cesari, S. Bicciato, et al., MICAL2isexpressedincancerassociatedneo-angiogeniccapillaryendotheliaandit is required for endothelial cell viability, motility and VEGF response, Biochim. This work was supported by the National Natural Science Biophys. Acta (BBA) - Mol. Basis Dis. 1865 (2019) 2111–2124. Foundation of China Grants (Nos. 81372515, 81572281, 81702278, [21] X.L. Jia, S.Y. Li, S.S. Dang, Y.A. Cheng, X. Zhang, W.J. Wang, et al., Increased ex- 81401901, 81802290, and 81974367), Innovation Programme of pression of chondroitin sulphate proteoglycans in rat hepatocellular carcinoma tissues, World J. Gastroenterol. 18 (2012) 3962–3976. Central South University (2020 CX043) and Scientific Assignment of [22] H. Yuan, B.L. Luo, B.M. He, [The effect of erythromycin on transforming growth Hunan Health Commission (C2019185). factor-beta(1)andsecretoryleukocyteproteinaseinhibitorinaratmodelofchronic obstructivepulmonarydisease],ZhonghuaJieheHeHuxiZazhi34(2011)523–527. [23] W. Yin, G. Tang, Q. Zhou, Y. Cao, H. Li, X. Fu, et al., Expression profile Analysis Declaration of competing interest identifies a novelfive-gene signature to improve prognosis prediction of glio- blastoma, Front. Genet. 10 (2019). [24] K. Friedrichs, S. Gluba, H. Eidtmann, W. Jonat, Overexpression of p53 and prog- The authors declare that they have no conflicts of interest. nosis in breast cancer, Cancer Am. Cancer Soc. 72 (1993) 3641–3647. [25] G.F. Ren, L. Tang, A.Q. Yang, W.W. Jiang, Y.M. Huang, Prognostic impact of Acknowledgements NDRG2 and NDRG3 in prostate cancer patients undergoing radical prostatectomy, Histol. Histopathol. 29 (2014) 535–542. [26] W. Wang, T. Shen, B. Dong, C.J. Creighton, Y. Meng, W. Zhou, et al., MAPK4 Our sincere appreciation goes out to all members of the Feng Yang overexpression promotes tumor progression via noncanonical activation of AKT/ lab for providing language assistance and technical guidance. Thank mTOR signaling, J. Clin. Invest. 129 (2019) 1015–1029. you to Wuyang Zhang and Jun Su for their language assistance. Thank [27] B. MacLean, D.M. Tomazela, N. Shulman, M. Chambers, G.L. Finney, B. Frewen, et al., Skyline: an open source document editor for creating and analyzing targeted youtoLiuliuandallotherfamilymembersfortheirencouragementand proteomics experiments, Bioinformatics 26 (2010) 966–968. support. [28] D. Gorlich, U. Kutay, Transport between the cell nucleus and the cytoplasm, Annu. Rev. Cell Dev. Biol. 15 (1999) 607–660. [29] N. Kudo, N. Matsumori, H. Taoka, D. Fujiwara, E.P. Schreiner, B. Wolff, et al., Appendix A. 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