Sự biến đổi sau dịch mã của Fascin: tác động đến sinh học tế bào và mối liên quan của nó với việc ức chế di căn khối u

Amino Acids - Tập 54 - Trang 1541-1552 - 2022
Nan-Li1, Zhi-Da Zhang1, Rong-Rong Li1, Jia-You Chen1, Hong-Xin Huang1, Yin-Wei Cheng1,2,3, Li-Yan Xu1,2,3, En-Min Li1
1The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
2Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou, China
3Institute of Basic Medical Science, Cancer Research Center, Shantou University Medical College, Shantou, China

Tóm tắt

Các biến đổi sau dịch mã (PTMs), đóng vai trò quan trọng trong việc điều chỉnh chức năng protein, có tiềm năng lớn như các dấu ấn sinh học về tình trạng ung thư. Fascin (protein bundling actin 1, FSCN1), một protein chính trong việc hình thành filopodia, có cấu trúc chủ yếu dựa trên các sợi actin (F-actin), có liên quan chặt chẽ đến sự xâm lấn và di căn của khối u. Các nghiên cứu đã tiết lộ nhiều cơ chế điều chỉnh khác nhau của Fascin ở người, bao gồm các PTMs. Mặc dù một số vị trí PTM của Fascin đã được xác định, nhưng chức năng chính xác và tầm quan trọng lâm sàng của chúng vẫn chưa được nghiên cứu kỹ lưỡng. Bài tổng quan này khám phá các nghiên cứu về chức năng của Fascin và ngắn gọn thảo luận về các cơ chế điều chỉnh của Fascin. Tiếp theo, để xem xét vai trò của các PTM của Fascin trong sinh học tế bào và mối liên quan của chúng với bệnh di căn, chúng tôi thảo luận về các tiến bộ trong việc đặc trưng các PTM của Fascin, bao gồm phosphoryl hóa, ubiquitin hóa, sumoyl hóa và acetyl hóa, cùng với các cơ chế điều chỉnh chính được thảo luận. Các PTM của Fascin có thể là những mục tiêu tiềm năng cho liệu pháp điều trị bệnh di căn.

Từ khóa

#Fascin #biến đổi sau dịch mã #bệnh di căn #sinh học tế bào #điều chỉnh protein

Tài liệu tham khảo

Abbasi A, Noroozinia F, Anvar S, Abbasi M, Hosseinzadeh S, Mokhtari S (2019) Fascin overexpression is associated with higher grades of breast cancer. Pol J Pathol : off J Pol Soc Pathol 70(4):264–268. https://doi.org/10.5114/pjp.2019.93128 Adams JC (2004) Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol 16(5):590–596. https://doi.org/10.1016/j.ceb.2004.07.009 Al-Saad K, Thorner P, Ngan BY, Gerstle JT, Kulkarni AV, Babyn P, Grant RM, Read S, Laxer RM, Chan HS (2005) Extranodal Rosai-Dorfman disease with multifocal bone and epidural involvement causing recurrent spinal cord compression. Pediatr Dev Pathol: off J Soc Pediatr Pathol Pediatr Pathol Soc 8(5):593–598. https://doi.org/10.1007/s10024-005-8102-6 Anilkumar N, Parsons M, Monk R, Ng T, Adams JC (2003) Interaction of fascin and protein kinase Calpha: a novel intersection in cell adhesion and motility. EMBO J 22(20):5390–5402. https://doi.org/10.1093/emboj/cdg521 Aramaki S, Mayanagi K, Jin M, Aoyama K, Yasunaga T (2016) Filopodia formation by crosslinking of F-actin with fascin in two different binding manners. Cytoskeleton (hoboken, NJ) 73(7):365–374. https://doi.org/10.1002/cm.21309 Barnawi R, Al-Khaldi S, Majed Sleiman G, Sarkar A, Al-Dhfyan A, Al-Mohanna F, Ghebeh H, Al-Alwan M (2016) Fascin is critical for the maintenance of breast cancer stem cell pool predominantly via the activation of the notch self-renewal pathway. Stem Cells 34(12):2799–2813. https://doi.org/10.1002/stem.2473 Chen Z, He N, Huang Y, Qin WT, Liu X, Li L (2018) Integration of a deep learning classifier with a random forest approach for predicting malonylation sites. Genom Proteom Bioinform 16(6):451–459. https://doi.org/10.1016/j.gpb.2018.08.004 Chen L, Liu S, Tao Y (2020) Regulating tumor suppressor genes: post-translational modifications. Signal Transduct Target Ther 5(1):90. https://doi.org/10.1038/s41392-020-0196-9 Chen C, Xie B, Li Z, Chen L, Chen Y, Zhou J, Ju S, Zhou Y, Zhang X, Zhuo W, Yang J, Mao M, Xu L, Wang L (2022) Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis. Cell Death Dis 13(2):150. https://doi.org/10.1038/s41419-022-04579-1 Cheng YW, Zeng FM, Li DJ, Wang SH, He JZ, Guo ZC, Nie PJ, Wu ZY, Shi WQ, Wen B, Xu XE, Liao LD, Li ZM, Wu JY, Zhan J, Zhang HQ, Chang ZJ, Zhang K, Xu LY, Li EM (2021) P300/CBP-associated factor (PCAF)-mediated acetylation of fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer. Cancer Commun (Lond, Engl) 41(12):1398–1416. https://doi.org/10.1002/cac2.12221 Chiang BY, Chou CC, Hsieh FT, Gao S, Lin JC, Lin SH, Chen TC, Khoo KH, Lin CH (2012) In vivo tagging and characterization of S-glutathionylated proteins by a chemoenzymatic method. Angew Chem Int Ed Engl 51(24):5871–5875. https://doi.org/10.1002/anie.201200321 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science (new York, NY) 325(5942):834–840. https://doi.org/10.1126/science.1175371 Colak G, Pougovkina O, Dai L, Tan M, Te Brinke H, Huang H, Cheng Z, Park J, Wan X, Liu X, Yue WW, Wanders RJ, Locasale JW, Lombard DB, de Boer VC, Zhao Y (2015) Proteomic and biochemical studies of lysine malonylation suggest its malonic aciduria-associated regulatory role in mitochondrial function and fatty acid oxidation. Mol Cell Proteom: MCP 14(11):3056–3071. https://doi.org/10.1074/mcp.M115.048850 Dalle-Donne I, Milzani A, Gagliano N, Colombo R, Giustarini D, Rossi R (2008) Molecular mechanisms and potential clinical significance of S-glutathionylation. Antioxid Redox Signal 10(3):445–473. https://doi.org/10.1089/ars.2007.1716 Dalle-Donne I, Rossi R, Colombo G, Giustarini D, Milzani A (2009) Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends Biochem Sci 34(2):85–96. https://doi.org/10.1016/j.tibs.2008.11.002 Elia AE, Boardman AP, Wang DC, Huttlin EL, Everley RA, Dephoure N, Zhou C, Koren I, Gygi SP, Elledge SJ (2015) Quantitative proteomic atlas of ubiquitination and acetylation in the DNA damage response. Mol Cell 59(5):867–881. https://doi.org/10.1016/j.molcel.2015.05.006 Fu H, Hu Z, Wen J, Wang K, Liu Y (2009) TGF-beta promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways. Acta Biochim Biophys Sin 41(8):648–656. https://doi.org/10.1093/abbs/gmp053 Gross C, Wiesmann V, Millen S, Kalmer M, Wittenberg T, Gettemans J, Thoma-Kress AK (2016) The tax-inducible actin-bundling protein Fascin is crucial for release and cell-to-cell transmission of human T-cell leukemia virus type 1 (HTLV-1). PLoS Pathog 12(10):e1005916. https://doi.org/10.1371/journal.ppat.1005916 Han S, Huang J, Liu B, Xing B, Bordeleau F, Reinhart-King CA, Li W, Zhang JJ, Huang XY (2016) Improving fascin inhibitors to block tumor cell migration and metastasis. Mol Oncol 10(7):966–980. https://doi.org/10.1016/j.molonc.2016.03.006 Han ZJ, Feng YH, Gu BH, Li YM, Chen H (2018) The post-translational modification, SUMOylation, and cancer (review). Int J Oncol 52(4):1081–1094. https://doi.org/10.3892/ijo.2018.4280 Hendriks IA, D’Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC (2014) Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol 21(10):927–936. https://doi.org/10.1038/nsmb.2890 Huang FK, Han S, Xing B, Huang J, Liu B, Bordeleau F, Reinhart-King CA, Zhang JJ, Huang XY (2015) Targeted inhibition of fascin function blocks tumor invasion and metastatic colonization. Nat Commun 6:7465. https://doi.org/10.1038/ncomms8465 Huang J, Dey R, Wang Y, Jakoncic J, Kurinov I, Huang XY (2018) structural insights into the induced-fit inhibition of fascin by a small-molecule inhibitor. J Mol Biol 430(9):1324–1335. https://doi.org/10.1016/j.jmb.2018.03.009 Jaiswal R, Breitsprecher D, Collins A, Corrêa IR Jr, Xu MQ, Goode BL (2013) The formin Daam1 and fascin directly collaborate to promote filopodia formation. Current Biology : CB 23(14):1373–1379. https://doi.org/10.1016/j.cub.2013.06.013 Jansen S, Collins A, Yang C, Rebowski G, Svitkina T, Dominguez R (2011) Mechanism of actin filament bundling by fascin. J Biol Chem 286(34):30087–30096. https://doi.org/10.1074/jbc.M111.251439 Jayo A, Malboubi M, Antoku S, Chang W, Ortiz-Zapater E, Groen C, Pfisterer K, Tootle T, Charras G, Gundersen GG, Parsons M (2016) Fascin regulates nuclear movement and deformation in migrating cells. Dev Cell 38(4):371–383. https://doi.org/10.1016/j.devcel.2016.07.021 Kane RE (1975) Preparation and purification of polymerized actin from sea urchin egg extracts. J Cell Biol 66(2):305–315. https://doi.org/10.1083/jcb.66.2.305 Kim KI, Baek SH, Chung CH (2002) Versatile protein tag, SUMO: its enzymology and biological function. J Cell Physiol 191(3):257–268. https://doi.org/10.1002/jcp.10100 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP (2011) Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol Cell 44(2):325–340. https://doi.org/10.1016/j.molcel.2011.08.025 Komander D, Rape M (2012) The ubiquitin code. Annu Rev Biochem 81:203–229. https://doi.org/10.1146/annurev-biochem-060310-170328 Lamptey J, Czika A, Aremu JO, Pervaz S, Adu-Gyamfi EA, Otoo A, Li F, Wang YX, Ding YB (2021) The role of fascin in carcinogenesis and embryo implantation. Exp Cell Res 409(1):112885. https://doi.org/10.1016/j.yexcr.2021.112885 Li A, Dawson JC, Forero-Vargas M, Spence HJ, Yu X, König I, Anderson K, Machesky LM (2010) The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr Biol: CB 20(4):339–345. https://doi.org/10.1016/j.cub.2009.12.035 Lin JC, Chiang BY, Chou CC, Chen TC, Chen YJ, Chen YJ, Lin CH (2015) Glutathionylspermidine in the modification of protein SH groups: the enzymology and its application to study protein glutathionylation. Mol (Basel, Switz) 20(1):1452–1474. https://doi.org/10.3390/molecules20011452 Lin S, Lu S, Mulaj M, Fang B, Keeley T, Wan L, Hao J, Muschol M, Sun J, Yang S (2016) Monoubiquitination inhibits the actin bundling activity of fascin. J Biol Chem 291(53):27323–27333. https://doi.org/10.1074/jbc.M116.767640 Lin S, Taylor MD, Singh PK, Yang S (2021) How does fascin promote cancer metastasis? FEBS J 288(5):1434–1446. https://doi.org/10.1111/febs.15484 Linares L, Kiernan R, Triboulet R, Chable-Bessia C, Latreille D, Cuvier O, Lacroix M, Le Cam L, Coux O, Benkirane M (2007) Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2. Nat Cell Biol 9(3):331–338. https://doi.org/10.1038/ncb1545 Liu H, Cui J, Zhang Y, Niu M, Xue X, Yin H, Tang Y, Dai L, Dai F, Guo Y, Wu Y, Gao W (2019) Mass spectrometry-based proteomic analysis of FSCN1-interacting proteins in laryngeal squamous cell carcinoma cells. IUBMB Life 71(11):1771–1784. https://doi.org/10.1002/iub.2121 Liu H, Zhang Y, Li L, Cao J, Guo Y, Wu Y, Gao W (2021a) Fascin actin-bundling protein 1 in human cancer: promising biomarker or therapeutic target? Mol Ther Oncolytics 20:240–264. https://doi.org/10.1016/j.omto.2020.12.014 Liu W, Xie L, He YH, Wu ZY, Liu LX, Bai XF, Deng DX, Xu XE, Liao LD, Lin W, Heng JH, Xu X, Peng L, Huang QF, Li CY, Zhang ZD, Wang W, Zhang GR, Gao X, Wang SH, Li CQ, Xu LY, Liu W, Li EM (2021b) Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting. Nat Commun. https://doi.org/10.1038/s41467-021-25202-5 Liu W, Cui YP, Liu W, Liu ZH, Xu LY, Li EM (2022) Deep proteome profiling promotes whole proteome characterization and drug discovery for esophageal squamous cell carcinoma. Cancer Biol Med 19(3):1–5. https://doi.org/10.20892/j.issn.2095-3941.2022.0024 Lu XF, Li EM, Du ZP, Xie JJ, Guo ZY, Gao SY, Liao LD, Shen ZY, Xie D, Xu LY (2010) Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation. Cell Mol Life Sci: CMLS 67(19):3313–3329. https://doi.org/10.1007/s00018-010-0382-y Machesky LM, Li A (2010) Fascin: invasive filopodia promoting metastasis. Commun Integr Biol 3(3):263–270. https://doi.org/10.4161/cib.3.3.11556 Mazzà D, Infante P, Colicchia V, Greco A, Alfonsi R, Siler M, Antonucci L, Po A, De Smaele E, Ferretti E, Capalbo C, Bellavia D, Canettieri G, Giannini G, Screpanti I, Gulino A, Di Marcotullio L (2013) PCAF ubiquitin ligase activity inhibits Hedgehog/Gli1 signaling in p53-dependent response to genotoxic stress. Cell Death Differ 20(12):1688–1697. https://doi.org/10.1038/cdd.2013.120 Meller R, Thompson SJ, Lusardi TA, Ordonez AN, Ashley MD, Jessick V, Wang W, Torrey DJ, Henshall DC, Gafken PR, Saugstad JA, Xiong ZG, Simon RP (2008) Ubiquitin proteasome-mediated synaptic reorganization: a novel mechanism underlying rapid ischemic tolerance. J Neurosci: off J Soc Neurosci 28(1):50–59. https://doi.org/10.1523/jneurosci.3474-07.2008 Nilufar S, Morrow AA, Lee JM, Perkins TJ (2013) FiloDetect: automatic detection of filopodia from fluorescence microscopy images. BMC Syst Biol 7:66. https://doi.org/10.1186/1752-0509-7-66 Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127(3):635–648. https://doi.org/10.1016/j.cell.2006.09.026 Ono S, Yamakita Y, Yamashiro S, Matsudaira PT, Gnarra JR, Obinata T, Matsumura F (1997) Identification of an actin binding region and a protein kinase C phosphorylation site on human fascin. J Biol Chem 272(4):2527–2533. https://doi.org/10.1074/jbc.272.4.2527 Orii T, Takeda H, Kawata S, Maeda K, Yamakawa M (2010) Differential immunophenotypic analysis of dendritic cell tumours. J Clin Pathol 63(6):497–503. https://doi.org/10.1136/jcp.2009.067819 Pfisterer K, Levitt J, Lawson CD, Marsh RJ, Heddleston JM, Wait E, Ameer-Beg SM, Cox S, Parsons M (2020) FMNL2 regulates dynamics of fascin in filopodia. J Cell Biol. https://doi.org/10.1083/jcb.201906111 Pickart CM (2001) Mechanisms underlying ubiquitination. Annu Rev Biochem 70:503–533. https://doi.org/10.1146/annurev.biochem.70.1.503 Povlsen L, Beli P, Wagner S, Poulsen S, Sylvestersen K, Poulsen J, Nielsen M, Bekker-Jensen S, Mailand N, ChoudharyCJNcb, (2012) Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Nat Cell Biol 14(10):1089–1098. https://doi.org/10.1038/ncb2579 Saad A, Bijian K, Qiu D, da Silva SD, Marques M, Chang CH, Nassour H, Ramotar D, Damaraju S, Mackey J, Bismar T, Witcher M, Alaoui-Jamali MA (2016) Insights into a novel nuclear function for fascin in the regulation of the amino-acid transporter SLC3A2. Sci Rep 6:36699. https://doi.org/10.1038/srep36699 Sheikh BN, Akhtar A (2019) The many lives of KATs - detectors, integrators and modulators of the cellular environment. Nat Rev Genet 20(1):7–23. https://doi.org/10.1038/s41576-018-0072-4 Snyder M, Huang XY, Zhang JJ (2011) Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration. J Biol Chem 286(45):38886–38893. https://doi.org/10.1074/jbc.M111.286245 Sun J, He H, Xiong Y, Lu S, Shen J, Cheng A, Chang WC, Hou MF, Lancaster JM, Kim M, Yang S (2011) Fascin protein is critical for transforming growth factor β protein-induced invasion and filopodia formation in spindle-shaped tumor cells. J Biol Chem 286(45):38865–38875. https://doi.org/10.1074/jbc.M111.270413 Sun J, He H, Pillai S, Xiong Y, Challa S, Xu L, Chellappan S, Yang S (2013) GATA3 transcription factor abrogates Smad4 transcription factor-mediated fascin overexpression, invadopodium formation, and breast cancer cell invasion. J Biol Chem 288(52):36971–36982. https://doi.org/10.1074/jbc.M113.506535 Taiyab A, Korol A, Deschamps PA, West-Mays JA (2016) β-Catenin/CBP-dependent signaling regulates TGF-β-induced epithelial to mesenchymal transition of lens epithelial cells. Invest Ophthalmol vis Sci 57(13):5736–5747. https://doi.org/10.1167/iovs.16-20162 Vignjevic D, Kojima S, Aratyn Y, Danciu O, Svitkina T, Borisy GG (2006) Role of fascin in filopodial protrusion. J Cell Biol 174(6):863–875. https://doi.org/10.1083/jcb.200603013 Vignjevic D, Schoumacher M, Gavert N, Janssen KP, Jih G, Laé M, Louvard D, Ben-Ze’ev A, Robine S (2007) Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Can Res 67(14):6844–6853. https://doi.org/10.1158/0008-5472.Can-07-0929 Wang T, Wang G, Zhang G, Hou R, Zhou L, Tian X (2021a) Systematic analysis of the lysine malonylome in Sanghuangporus sanghuang. BMC Genom 22(1):840. https://doi.org/10.1186/s12864-021-08120-0 Wang Y, Song M, Liu M, Zhang G, Zhang X, Li MO, Ma X, Zhang JJ, Huang XY (2021b) Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity. Cell Rep 35(1):108948. https://doi.org/10.1016/j.celrep.2021.108948 Weinert BT, Schölz C, Wagner SA, Iesmantavicius V, Su D, Daniel JA, Choudhary C (2013) Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep 4(4):842–851. https://doi.org/10.1016/j.celrep.2013.07.024 Wiener R, Zhang X, Wang T, Wolberger C (2012) The mechanism of OTUB1-mediated inhibition of ubiquitination. Nature 483(7391):618–622. https://doi.org/10.1038/nature10911 Wu X, Wen B, Lin L, Shi W, Li D, Cheng Y, Xu LY, Li EM, Dong G (2021) New insights into the function of fascin in actin bundling: a combined theoretical and experimental study. Int J Biochem Cell Biol 139:106056. https://doi.org/10.1016/j.biocel.2021.106056 Yamakita Y, Ono S, Matsumura F, Yamashiro S (1996) Phosphorylation of human fascin inhibits its actin binding and bundling activities. J Biol Chem 271(21):12632–12638. https://doi.org/10.1074/jbc.271.21.12632 Yamashiro-Matsumura S, Matsumura F (1985) Purification and characterization of an F-actin-bundling 55-kilodalton protein from HeLa cells. J Biol Chem 260(8):5087–5097 Yang S, Huang FK, Huang J, Chen S, Jakoncic J, Leo-Macias A, Diaz-Avalos R, Chen L, Zhang JJ, Huang XY (2013) Molecular mechanism of fascin function in filopodial formation. J Biol Chem 288(1):274–284. https://doi.org/10.1074/jbc.M112.427971 Yang J, Zhang N, Gao R, Zhu Y, Zhang Z, Xu X, Wang J, Li Z, Liu X, Li Z, Li J, Bi J, Kong C (2018) TGF-β1 induced fascin1 expression facilitates the migration and invasion of kidney carcinoma cells through ERK and JNK signaling pathways. Biochem Biophys Res Commun 501(4):913–919. https://doi.org/10.1016/j.bbrc.2018.05.081 Zanet J, Jayo A, Plaza S, Millard T, Parsons M, Stramer B (2012) Fascin promotes filopodia formation independent of its role in actin bundling. J Cell Biol 197(4):477–486. https://doi.org/10.1083/jcb.201110135 Zeng FM, Wang XN, Shi HS, Xie JJ, Du ZP, Liao LD, Nie PJ, Xu LY, Li EM (2017) Fascin phosphorylation sites combine to regulate esophageal squamous cancer cell behavior. Amino Acids 49(5):943–955. https://doi.org/10.1007/s00726-017-2398-1 Zeng F, Cheng Y, He J, Xu X, Liao L, Xu L, Li E-M (2022) Fascin lysine 471 acetylation cooperates with serine 39 phosphorylation to inhibit actin-bundling activity and tumor metastasis in esophageal squamous cell carcinoma. Cancer Commun (lond, Engl). https://doi.org/10.1002/cac2.12297 Zhang F-R, Tao L-H, Shen Z-Y, Lv Z, Xu L-Y, Li E-M (2008) Fascin expression in human embryonic, fetal, and normal adult tissue. J Histochem Cytochem 56(2):193–199. https://doi.org/10.1369/jhc.7A7353.2007 Zhang ZD, Wen B, Li DJ, Deng DX, Wu XD, Cheng YW, Liao LD, Long L, Dong G, Xu LY, Li EM (2022) AKT Serine/Threonine Kinase 2-mediated phosphorylation of Fascin Threonine 403 regulates esophageal cancer progression. The Int J Biochem Cell Biol 145:106188. https://doi.org/10.1016/j.biocel.2022.106188 Zhao Q, Shen JH, Shen ZY, Wu ZY, Xu XE, Xie JJ, Wu JY, Huang Q, Lu XF, Li EM, Xu LY (2010) Phosphorylation of fascin decreases the risk of poor survival in patients with esophageal squamous cell carcinoma. J Histochem Cytochem: off J Histochem Soc 58(11):979–988. https://doi.org/10.1369/jhc.2010.955765 Zhao X, Gao S, Ren H, Sun W, Zhang H, Sun J, Yang S, Hao J (2014) Hypoxia-inducible factor-1 promotes pancreatic ductal adenocarcinoma invasion and metastasis by activating transcription of the actin-bundling protein fascin. Can Res 74(9):2455–2464. https://doi.org/10.1158/0008-5472.Can-13-3009 Zhao W, Gao J, Wu J, Liu QH, Wang ZG, Li HL, Xing LH (2015) Expression of fascin-1 on human lung cancer and paracarcinoma tissue and its relation to clinicopathological characteristics in patients with lung cancer. Onco Targets Ther 8:2571–2576. https://doi.org/10.2147/ott.S81915