角蛋白在胃肠道肿瘤中的作用和研究进展

doi:10.24920/003990

摘要/Abstract

摘要：

胃肠道肿瘤的发病率和死亡率居高不下。尽管诊断和治疗技术在不断改进,胃肠道肿瘤的早期诊断、中期和晚期治疗、药物耐受性以及癌症复发和转移等问题仍构成巨大挑战。在本篇综述中,我们总结了角蛋白在胃肠道肿瘤中的作用和研究进展,希望它们能成为预测、诊断或治疗胃肠道肿瘤的有效生物标志物。

关键词: 角蛋白, 胃肠道肿瘤, 诊断意义, 机制

Abstract:

The incidence and mortality rates of gastrointestinal (GI) cancer remain high. Despite constant improvements in diagnostic and therapeutic techniques, the early diagnosis, mid- and late-stage treatment, drug tolerance, and cancer recurrence and metastasis in GI cancer remain challenging. In this review article we summarize the recent research advance in the roles of keratins in GI cancer, with the hope that they will become efficient biomarkers for the prediction, diagnosis, or treatment of these malignancies.

Key words: Keratin, gastrointestinal cancer, diagnostic significance, mechanism

基金资助: 吴阶平医学基金会(320.6750.19020)

Siwen Ouyang, Weiming Kang. Research Advances in the Role of Keratins in Gastrointestinal Cancer[J].Chinese Medical Sciences Journal, 2022, 37(1): 73-78.

参考文献 42.

1.	Waschke J. The desmosome and pemphigns. Histochem Cell Biol 2008; 130(1):21-54. doi: 10.1007/s00418-008-0420-0. doi: 10.1007/s00418-008-0420-0 pmid: 18386043
2.	Chai Junhui, Zhang Zhandong, Ma Qi, et al. The expression and significance of CK18 in gastric cancer and regional metastatic lymph nodes. Henan Med Res 2014; 23(9):1-4. Chinese. doi: 10.3969/j.issn.1004-437X2014.09.001. doi: 10.3969/j.issn.1004-437X2014.09.001
3.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6):394-424. doi: 10.3322/caac.21492. doi: 10.3322/caac.21492
4.	Zou WB, Li ZS. Research progress in the incidence and mortality of gastric cancer in China. Chin J Practic Intern Med 2014; 34(4):408-15. Chinese. doi: CNKI:SUN:SYNK.0.2014-04-034. doi: CNKI:SUN:SYNK.0.2014-04-034
5.	National Health Commission. Regulations for Diagnosis and Treatment of Gastric Cancer (2018 Edition). Chin J Digest Med Image, 2019; 9(3):118-144. Chinese. doi: 10.3877/cma.j.issn.2095-2015.2019.03.008. doi: 10.3877/cma.j.issn.2095-2015.2019.03.008
6.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1):7-34. doi: 10.3322/caac.21551. doi: 10.3322/caac.21551
7.	Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin 2017; 67(3):177-93. doi: 10.3322/caac.21395. doi: 10.3322/caac.21395
8.	Omary MB, Ku NO, Strnad P, et al. Toward unraveling the complexity of simple epithelial keratins in human disease. J Clin Invest 2009; 119(7):1794-805. doi: 10.1172/JCI37762. doi: 10.1172/JCI37762
9.	Bragulla HH, Homberger DG. Structure and functions of keratin proteins in simple, stratifed, keratinized and cornifed epithelia. J Anat 2009; 214(4):516-59. doi: 10.1083/jcb.101.4.1257. doi: 10.1111/j.1469-7580.2009.01066.x pmid: 19422428
10.	Gu LH, Coulombe PA. Keratin function in skin epithelia: A broadening palette with surprising shades. Curr Opin Cell Biol 2007; 19(1):13-23. doi: 10.1016/j.ceb.2006.12.007. doi: 10.1016/j.ceb.2006.12.007
11.	Magin TM, Vijayaraj P, Leube RE. Structural and regulatory functions of keratins. Exp Cell Res 2007; 313(10):2021-32. doi: 10.1016/j.yexcr.2007.03.005. doi: 10.1016/j.yexcr.2007.03.005
12.	Zatloukal K, French SW, Stumptner C, et al. From Mallory to Mallory-Denk bodies: What, how and why? Exp Cell Res 2007; 313(10):2033-49. doi: 10.1016/j.yexcr.2007.04.024. doi: 10.1016/j.yexcr.2007.04.024 pmid: 17531973
13.	Fingar DC, Blenis J. Target of rapamycin (TOR): An integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 2004; 23(18):3151-71. doi: 10.1038/sj.onc.1207542. doi: 10.1038/sj.onc.1207542 pmid: 15094765
14.	Kim S, Wong P, Coulombe PA. A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. Nature 2006; 441(7091):362-5. doi: 10.1038/nature04659. doi: 10.1038/nature04659
15.	Ku NO, Omary MB. A disease- and phosphorylation-related nonmechanical function for keratin 8. J Cell Biol 2006; 174(1):115-25. doi: 10.1083/jcb.200602146. doi: 10.1083/jcb.200602146
16.	Takano J, Morishita A, Fujihara S, et al. Galectin-9 suppresses the proliferation of gastric cancer cells in vitro. Oncol Rep 2016; 35(2):851-60. doi: 10.3892/or.2015.4452. doi: 10.3892/or.2015.4452
17.	Sequeira I, Neves J, Carrero D, et al. Immunomodulatory role of Keratin 76 in oral and gastric cancer. Nat Commun 2018; 9(1):3437. doi: 10.1038/s41467-018-05872-4. doi: 10.1038/s41467-018-05872-4 pmid: 30143634
18.	Fortier AM, van Themsche C, Asselin E, et al. Akt isoforms regulate intermediate flament protein levels in epithelial carcinoma cells. FEBS Lett 2010; 584(5):984-8. doi: 10.1016/j.febslet.2010.01.045. doi: 10.1016/j.febslet.2010.01.045
19.	Vijayaraj P, Kröger C, Reuter U, et al. Keratins regulate protein biosynthesis through localization of GLUT1 and-3 upstream of AMP kinase and Raptor. J Cell Biol 2009; 187(2):175-84. doi: 10.1083/jcb.200906094. doi: 10.1083/jcb.200906094 pmid: 19841136
20.	Busch T, Armacki M, Eiseler T, et al. Keratin 8 phosphorylation regulates keratin reorganization and migration of epithelial tumor cells. J Cell Sci 2012; 125(Pt 9):2148-59. doi: 10.1242/jcs.080127. doi: 10.1242/jcs.080127
21.	Moll R, Divo M, Langbein L. The human keratins: Biology and pathology. Histochem Cell Biol 2008; 129(6):705-33. doi: 10.1007/s00418-008-0435-6. doi: 10.1007/s00418-008-0435-6
22.	Mihaela CE, Denisa LD, Laura GN, et al. Knockdown of KRT17 by siRNA induces antitumoral effects on gastric cancer cells. Gastric Cancer 2017; 20(6):948-59. doi: 10.1007/s10120-017-0712-y. doi: 10.1007/s10120-017-0712-y
23.	Maeda S, Otsuka M, Hirata Y, et al. cDNA Microarray Analysis of Helicobacter pyloriMediated Alteration of Gene Expression in Gastric Cancer Cells. Biochem Biophys Res Commun 2001; 284(2):443-9. doi: 10.1006/bbrc.2001.5006. doi: 10.1006/bbrc.2001.5006
24.	Wa’el El-Rifai, Christopher AM, Mohammad KA, et al. Gastric cancers overexpress S100A calcium-binding proteins. Cancer Res 2002; 62(23):6823-6. doi: 10.1097/00002820-200212000-00014. doi: 10.1097/00002820-200212000-00014 pmid: 12460893
25.	You XL, Wang YJ, Wu J, et al. Aberrant Cytokeratin 20 mRNA Expression in Peripheral Blood and Lymph Nodes Indicates Micrometastasis and Poor Prognosis in Patients With Gastric Carcinoma. Technol Cancer Res Treat 2019; 18:1533033819832856. doi: 10.1177/1533033819832856. doi: 10.1177/1533033819832856
26.	Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology 2002; 40(5):403-39. doi: 10.1046/j.1365-2559.2002.01387.x. doi: 10.1046/j.1365-2559.2002.01387.x pmid: 12010363
27.	Chen WJ, Zhang WT, Wu RS, et al. Identification of biomarkers associated with histological grade and prognosis of gastric cancer by co-expression network analysis. Oncol Lett 2019; 18(5):5499-507. doi: 10.3892/ol.2019.10869. doi: 10.3892/ol.2019.10869
28.	Craig A M, Sara K, James M C, et al. Metachronous serrated neoplasia is uncommon after right colectomy in patients with methylator colon cancers with a high degree of microsatellite instability. Dis Colon Rectum 2014; 57(1):39-46. doi: 10.1097/01.dcr.0000437690.18709.76. doi: 10.1097/01.dcr.0000437690.18709.76
29.	Tadashi Terada. An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: I. Cytokeratin profile in 42 cases. Int J Clin Exp Pathol 2013; 6(4):703-10. doi: 10.2147/OTT.S28155. doi: 10.2147/OTT.S28155
30.	Nileema K, Samrat T K, Lalit S, et al. Plakophilin3 loss leads to an increase in PRL3 levels promoting K8 dephosphorylation, which is required for transformation and metastasis. PLoS One 2012; 7(6):e38561. doi: 10.1371/journal.pone.0038561. doi: 10.1371/journal.pone.0038561
31.	Julia O M, Iris A K, Joel H N, et al. Keratin 8-deletion induced colitis predisposes to murine colorectal cancer enforced by the inflammasome and IL-22 pathway. Carcinogenesis 2016; 37(8):777-786. doi: 10.1093/carcin/bgw063. doi: 10.1093/carcin/bgw063
32.	Zhang NN, Zhang R, Zou K, et al. Keratin 23 promotes telomerase reverse transcriptase expression and human colorectal cancer growth. Cell Death Dis 2017 ; 8(7):e2961. doi: 10.1038/cddis.2017.339. doi: 10.1038/cddis.2017.339
33.	Samuel A, Yoku H, Ashlesha M, et al. Krt19(+)/Lgr5(-) Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine. Cell Stem Cell 2015; 16(6):627-38. doi: 10.1016/j.stem.2015.04.013 doi: 10.1016/j.stem.2015.04.013 pmid: 26046762
34.	Hunain A, Lalit S, Samrat T K, et al. Novel function of keratins 5 and 14 in proliferation and differentiation of stratified epithelial cells. Mol Biol Cell 2011; 22(21):4068-78. doi: 10.1091/mbc.E10-08-0703. doi: 10.1091/mbc.E10-08-0703 pmid: 21900500
35.	Abdul Q K, Jonathan P B, Steven R B, et al. Keratin 8 expression in colon cancer associates with low faecal butyrate levels. BMC Gastroenterol 2011; 11:2. doi: 10.1186/1471-230X-11-2. doi: 10.1186/1471-230X-11-2 pmid: 21219647
36.	Yasuo I, Hidetsugu Y, Kazunori F, et al. Expression of cytokeratin 20 indicates invasive histological phenotype in poorly differentiated colorectal adenocarcinoma. Anticancer Res 2014; 34(1):159-67. doi: 10.1016/j.lungcan.2013.10.009. doi: 10.1016/j.lungcan.2013.10.009 pmid: 24403457
37.	Hidetsugu Y, Yasuo I, Takuya O, et al. Aberrant cytokeratin expression as a possible prognostic predictor in poorly differentiated colorectal carcinoma. J Gastroenterol Hepatol 2013; 28(12):1815-22. doi: 10.1111/jgh.12319. doi: 10.1111/jgh.12319
38.	Aida H, Diana M T, Asghar MN, et al. Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon. Proc Natl Acad Sci U S A 2011; 108(4):1445-50. doi: 10.1073/pnas.1010833108. doi: 10.1073/pnas.1010833108
39.	Wang YB, Ma SX, Huang YN, et al. The clinical value of serum CK18 and CA19-9 detection in patients with rectal cancer. J Radioimmunol 2012; 25(2):151. Chinese. doi: 10.3969/j.issn.1008-9810.2012.02.019. doi: 10.3969/j.issn.1008-9810.2012.02.019
40.	Yang RN, Yang SH, Chang CC, et al. Upregulation of fecal cytokeratin 19 is associated with prognosis in older colorectal cancer patients. Genet Test Mol Biomarkers 2010; 14(5):703-8. doi: 10.1089/gtmb.2010.0047. doi: 10.1089/gtmb.2010.0047
41.	Berrin T, Gulcin T, Gulsah C, et al. Overexpression of CK20, MAP3K8 and EIF5A correlates with poor prognosis in early-onset colorectal cancer patients. J Cancer Res Clin Oncol 2013; 139(4):691-702. doi: 10.1007/s00432-013-1372-x. doi: 10.1007/s00432-013-1372-x pmid: 23322277
42.	Šamija I, Josip L, Mirjana KM, et al. Detection of cytokeratin-20-positive cells in preoperative and postoperative blood samples from colorectal cancer patients by real-time RT-PCR. Int J Biol Markers 2013; 28(2):174-81. doi: 10.5301/jbm.5000003. doi: 10.5301/jbm.5000003 pmid: 23558939

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