食管癌干细胞特性及相关蛋白的研究进展

doi:10.3969/j.issn.1004-616x.2023.03.013

摘要/Abstract

摘要： 肿瘤干细胞学说是一种与肿瘤相关的新学说，该学说认为肿瘤组织中有极少量的肿瘤干细胞，具备自我更新及无限增殖的能力，在促进肿瘤发生和维持肿瘤发展及治疗抵抗中起着至关重要的作用。食管癌的复发、转移与耐药被认为与肿瘤干细胞密切相关。目前，针对特定位点的分子靶向药物在恶性肿瘤的治疗中取得了一定的临床疗效，因此全面了解影响食管癌干细胞的相关机制，并进行针对性的干预，可能会杀灭食管癌干细胞，提高食管癌的临床疗效。本文就食管癌干细胞特性及相关蛋白的研究进展进行综述。

关键词: 食管癌干细胞, 信号通路, 上皮-间充质转化, 微环境, 细胞静止状态, DNA损伤抵抗

中图分类号:

R735.1

闫俊涛, 李洪霖, 朱亚辉, 常思思, 高付彦, 马纯政. 食管癌干细胞特性及相关蛋白的研究进展[J]. 癌变·畸变·突变, 2023, 35(3): 228-230.

参考文献

[1] UHLENHOPP D J, THEN E O, SUNKARA T, et al. Epidemiology of esophageal cancer:update in global trends, etiology and risk factors[J]. Clin J Gastroenterol, 2020, 13(6):1010-1021.
[2] 刘宗超, 李哲轩, 张阳, 等. 2020全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2021, 7(2):1-13.
[3] 郑鑫林, 夏学阳, 张金周, 等. 食管癌干细胞相关标记物及其分离和鉴定的研究进展[J]. 癌变·畸变·突变, 2016, 28(3):246-248.
[4] MARIE-EGYPTIENNE D T, LOHSE I, HILL R P. Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance:potential role of hypoxia[J]. Cancer Lett, 2013, 341(1):63-72.
[5] QIAN X, TAN C, WANG F, et al. Esophageal cancer stem cells and implications for future therapeutics[J]. Onco Targets Ther, 2016, 9:2247-2254.
[6] ROBEY R W, POLGAR O, DEEKEN J, et al. ABCG2:determining its relevance in clinical drug resistance[J]. Cancer Metastasis Rev, 2007, 26(1):39-57.
[7] ROSS D D, NAKANISHI T. Impact of breast cancer resistance protein on cancer treatment outcomes[J]. Methods Mol Biol, 2010, 596:251-290.
[8] WANG D, PLUKKER J T M, COPPES R P. Cancer stem cells with increased metastatic potential as a therapeutic target for esophageal cancer[J]. Semin Cancer Biol, 2017, 44:60-66.
[9] HUANG L J, LU Q, HAN Y, et al. ABCG2/V-ATPase was associated with the drug resistance and tumor metastasis of esophageal squamous cancer cells[J]. Diagn Pathol, 2012, 7:180.
[10] TENG Y, YU X Y, YUAN H, et al. DNMT1 ablation suppresses tumorigenesis by inhibiting the self-renewal of esophageal cancer stem cells[J]. Oncotarget, 2018, 9(27):18896-18907.
[11] 滕颖. 食管癌干细胞DNA甲基化谱及相关基因DNMT1功能的研究[D]. 北京:北京协和医学院, 2017.
[12] HONEYWELL R J, SARKISJAN D, KRISTENSEN M H, et al. DNA methyltransferases expression in normal tissues and various human cancer cell lines, xenografts and tumors[J]. Nucleic Acids, 2018, 37(12):696-708.
[13] ARNOUK H, YUM G, SHAH D. Cripto-1 as a key factor in tumor progression, epithelial to mesenchymal transition and cancer stem cells[J]. Int J Mol Sci, 2021, 22(17):9280.
[14] ARBORETTO P, CILLO M, LEONARDI A. New insights into cancer targeted therapy:nodal and cripto-1 as attractive candidates[J]. Int J Mol Sci, 2021, 22(15):7838.
[15] XU C H, ZOU J, LI L, et al. Elevated serum Cripto-1 and VEGF levels in patients with non-small cell lung cancer[J]. FASEB Bioadv, 2022, 4(8):539-546.
[16] LIU Q, CUI X, YU X, et al. Cripto-1 acts as a functional marker of cancer stem-like cells and predicts prognosis of the patients in esophageal squamous cell carcinoma[J]. Mol Cancer, 2017, 16(1):81.
[17] 宋爽, 徐琳琳. 表面标志物Cripto-1表达对食管癌干细胞生长的作用机制研究[J]. 蚌埠医学院学报, 2017, 42(10):1313-1317.
[18] DANIEL S K, SEO Y D, PILLARISETTY V G. The CXCL12-CXCR4/CXCR7 axis as a mechanism of immune resistance in gastrointestinal malignancies[J]. Semin Cancer Biol, 2020, 65:176-188.
[19] WU X X, ZHANG H D, SUI Z L, et al. The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma[J]. Cancer Biol Med, 2021, 18(2):401-410.
[20] WANG X W, CAO Y, ZHANG S R, et al. Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer[J]. Oncotarget, 2017, 8(22):36149-36160.
[21] SONG S M, AJANI J A, HONJO S, et al. Hippo coactivator YAP1 upregulates SOX9 and endows esophageal cancer cells with stem-like properties[J]. Cancer Res, 2014, 74(15):4170-4182.
[22] WEI H L, WANG F H, WANG Y, et al. Verteporfin suppresses cell survival, angiogenesis and vasculogenic mimicry of pancreatic ductal adenocarcinoma via disrupting the YAP-TEAD complex[J]. Cancer Sci, 2017, 108(3):478-487.
[23] WANG L H, ZHANG Z Y, YU X D, et al. Unbalanced YAP-SOX9 circuit drives stemness and malignant progression in esophageal squamous cell carcinoma[J]. Oncogene, 2019, 38(12):2042-2055.
[24] CLOOS P A, CHRISTENSEN J, AGGER K, et al. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3[J]. Nature, 2006, 442(7100):307-311.
[25] 贾瑞诺. 组蛋白去甲基化酶GASC1维持食管癌肿瘤干细胞及其抑制剂抗肿瘤分子机制研究[D]. 郑州:郑州大学, 2019.
[26] JIA R N, YANG L, YUAN X, et al. GASC1 promotes stemness of esophageal squamous cell carcinoma via NOTCH1 promoter demethylation[J]. J Oncol, 2019, 2019:1621054.
[27] KALLURI R, WEINBERG R A. The basics of epithelial-mesenchymal transition[J]. J Clin Invest, 2009, 119(6):1420-1428.
[28] THIERY J P. Epithelial-mesenchymal transitions in tumour progression[J]. Nat Rev Cancer, 2002, 2(6):442-454.
[29] LIU X J, HE M J, LI L L, et al. EMT and cancer cell stemness associated with chemotherapeutic resistance in esophageal cancer[J]. Front Oncol, 2021, 11:672222.
[30] SCHATTON T, FRANK M H. Cancer stem cells and human malignant melanoma[J]. Pigment Cell Melanoma Res, 2008, 21(1):39-55.
[31] 刘灵. 缺氧在食管鳞癌细胞上皮-间质转化及干细胞化中的作用[D]. 郑州:郑州大学, 2015.
[32] FLEMING H E, JANZEN V, CELSO C L, et al. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo[J]. Cell Stem Cell, 2008, 2(3):274-283.
[33] CHEN Y L, LI D, WANG D P, et al. Quiescence and attenuated DNA damage response promote survival of esophageal cancer stem cells[J]. J Cell Biochem, 2012, 113(12):3643-3652.