[1]龙佑梅,黄梨,王艳清,等.CD44v6通过ERK途径促进子宫内膜癌的 增殖和转移[J].中国计划生育和妇产科,2020,(7):76-79.
　LONG Youmei,HUANG Li,WANG Yanqing,et al.CD44v6 promote the proliferation and metastasis of endometrial cancer by ERK pathway[J].Chinese Journal of Family Planning & Gynecotokology,2020,(7):76-79.
点击复制

CD44v6通过ERK途径促进子宫内膜癌的 增殖和转移
分享到：

《中国计划生育和妇产科》[ISSN:1674-4020/CN:51-1708/R]

卷:
期数:
2020年7期
页码:
76-79
栏目:
妇科产科热点研究
出版日期:
2020-07-25

文章信息/Info

Title:
CD44v6 promote the proliferation and metastasis of endometrial cancer by ERK pathway
作者:
龙佑梅; 黄梨; 王艳清; 夏良斌*
武汉大学人民医院妇二科
Author(s):
LONG Youmei; HUANG Li; WANG Yanqing; XIA Liangbin*
Department of Gynecology,People's Hospital of Wuhan University,Wuhan Hubei 430060,P.R.China
关键词:
子宫内膜癌; 粘附分子; CD44v6; pERK
Keywords:
endometrial cancer; adhesion molecules; CD44v6; pERK
分类号:
R 73733
摘要:
目的探究CD44v6的表达水平是否与子宫内膜癌(endometrial carcinoma，EC)的进展有关，并探讨其分子途径和生物学过程。方法收集2017年1月至2018年12月在武汉大学人民医院妇产科接受分期手术的30例手术标本，包括EC及距离癌组织2 cm处的癌旁非肿瘤内膜组织，采用免疫组织化学染色法检测CD44v6、ERK和磷酸化ERK(pERK)在EC组织中的表达。采用实时定量聚合酶链反应检测CD44v6在EC组织和细胞系中的表达，蛋白质印迹法检测相关蛋白的表达，最后进行克隆、迁移和侵袭试验。结果CD44v6和pERK在EC组织中的表达明显增强。Western blot及PCR结果显示siCD44v6可明显抑制CD44v6的表达，当CD44v6的表达受到抑制后，pERK的蛋白水平也降低。细胞克隆、转移和侵袭实验结果显示，抑制CD44v6表达可以抑制Ishikawa 细胞的克隆、增殖和侵袭能力，但是可以通过ERK激动剂来逆转这种效果。结论CD44v6在EC组织中高表达，且能够通过促进ERK蛋白磷酸化，从而促进EC的侵袭和转移，导致EC患者不良的预后。推测阻断CD44v6与ERK通路的传导是治疗EC的潜在方法。
Abstract:
ObjectiveTo investigate whether the expression level of CD44v6 is related to the progress of endometrial carcinoma (EC), and to explore its molecular pathways and biological processes.MethodsA total of 30 surgical specimens, including EC and nontumor endometrial tissues adjacent to the cancer tissue 2 cm away from the cancer tissue, were collected from January 2017 to December 2018 in the staged surgery in Department of Obstetrics and Gynecology of People's Hospital of Wuhan University. Immunohistochemical staining was used to detect CD44v6,ERK and phosphorylated ERK (pERK) expression in EC tissues. Realtime quantitative polymerase chain reaction was used to detect the expression of CD44v6 in EC tissues and cell lines. Western blot was used to detect the expression of related proteins. Finally, cloning, transwell and invasion tests were performed. ResultsThe expression of CD44v6 and pERK in EC tissues was significantly enhanced. Western blot and PCR results showed that siCD44v6 can significantly inhibit the expression of CD44v6. When the expression of CD44v6 was suppressed, the protein level of pERK also decreased. The results of cell cloning, metastasis and invasion experiments showed that inhibition of CD44v6 expression can inhibit the cloning, proliferation and invasion ability of Ishikawa cells, but this effect can be reversed by ERK agonists. ConclusionCD44v6 is highly expressed in EC tissues, and it can promote the invasion and metastasis of EC by promoting ERK protein phosphorylation, leading to poor prognosis of EC patients. It is speculated that blocking the conduction of CD44v6 and ERK pathway is a potential treatment for EC

参考文献/References:

［1］Schrauwen S,Depreeuw J,Coenegrachts L,et al.Dual blockade of PI3K/AKT/mTOR (NVPBEZ235) and Ras/Raf/MEK (AZD6244) pathways synergistically inhibit growth of primary endometrioid endometrial carcinoma cultures, whereas NVPBEZ235 reduces tumor growth in the corresponding xenograft models ［J］. Gynecologic Oncology, 2015, 138(1): 165173. ［2］Mizumoto Y, Kyo S, Noriko M, et al. Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis ［J］. Cancer Science, 2007, 98(5): 652658. ［3］O Mara T A, Glubb D M, Amant F, et al. Identification of nine new susceptibility loci for endometrial cancer ［J］. Nature Communications, 2018,9(1):3166. ［4］Hoshimoto K, Yamauchi N, Takazawa Yutaka, et al. CD44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker ［J］. Pathology Research and Practice, 2003, 199(2): 7177. ［5］Soon C H, Jae Y S, Jae K L, et al. Significance of CD44v6 expression in gynecologic malignancies ［J］. Journal of Obstetrics and Gynaecology Research, 2006, 32(4): 379386. ［6］KansuCelik H, Gungor M, Firat O, et al. Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue ［J］. Archives of Gynecology and Obstetrics, 2017, 296(2): 313318. ［7］Du Pengcheng, Liang Haibin, Fu Xiaowei, et al. SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer ［J］. Cancer Cell International, 2019, 19(1):33. ［8］Wang Yingmei, Zhu Yuanxi, Zhang Lizhi, et al. Insulin promotes proliferation, survival, and invasion in endometrial carcinoma by activating the MEK/ERK pathway ［J］. Cancer Letters, 2012, 322(2): 223231. ［9］Deng Wenjie,Wang Yueyuan,Shuo Zhao,et al.MICAL1 facilitates breast cancer cell proliferation via ROSsensitive ERK/cyclin D pathway ［J］. Journal of Cellular and Molecular Medicine, 2018, 22(6): 31083118. ［10］Cun Wang, Jin Haojie, Gao Dongmei, et al. PhosphoERK is a biomarker of response to a synthetic lethal drug combination of sorafenib and MEK inhibition in liver cancer ［J］. Journal of Hepatology, 2018, 69(5): 10571065. ［11］Sebastian S R, Taylor J B, Jonathan S L, et al. Activated ERK1/2 increases CD44 in glomerular parietal epithelial cells leading to matrix expansion ［J］. Kidney International, 2017, 91(4): 896913. ［12］Takashi M,Dong Peixin,Ihira K,et al.Moleculartargeted therapies and precision medicine for endometrial cancer ［J］. Japanese Journal of Clinical Oncology, 2019, 49(2): 108120. ［13］Gao Shenglan, Lin Ziying, Li Chunyan, et al. lncINSIGF2 promotes cell proliferation and migration by promoting G1/S transition in lung cancer ［J］.Technology in Cancer Research & Treatment,2019,18(1):153303381882302. ［14］Merheb R, AbdelMassih R M, Karam M C. Immunomodulatory effect of natural and modified Citrus pectin on cytokine levels in the spleen of BALB/c mice ［J］. International Journal of Biological Macromolecules, 2019, 121: 15. ［15］Wu Yong,Yu Xiaoting,Yi Xianghua,et al.Aberrant phosphorylation of SMAD4 Thr277Mediated USP9xSMAD4 interaction by free fatty acids promotes breast cancer metastasis ［J］. Cancer Research, 2017, 77(6): 13831394. ［16］Quan Zhou,Ling Rhan,Yang Xzhou,et al. MiR195 suppresses cervical cancer migration and invasion through targeting Smad3 ［J］. International Journal of Gynecologic Cancer, 2016, 26(5): 817824. ［17］Ke Wu, Yu Xiaoting, Huang Zhimin, et al. Targeting of PP2Cδ by a small molecule C23 inhibits high glucoseinduced breast cancer progression in vivo ［J］. Antioxidants & Redox Signaling, 2019, 30(17): 19831998. ［18］Zheng Yinli, Lei Li, Jia Yongxun, et al. LINC01554Mediated glucose metabolism reprogramming suppresses tumorigenicity in hepatocellular carcinoma via downregulating PKM2 expression and inhibiting Akt/mTOR signaling pathway ［J］. Theranostics, 2019, 9(3): 796810. ［19］RaglaN O, Kalliala I, Markozannes G, et al. Risk factors for endometrial cancer: An umbrella review of the literature ［J］. International Journal of Cancer, 2019, 145(7): 17191730. ［20］Jing Xue, Lei Li, Na Li, et al. Metformin suppresses cancer cell growth in endometrial carcinoma by inhibiting PDL1 ［J］. European Journal of Pharmacology, 2019, 859: 172541. ［21］Wang Yanqing, Xiao Yang, Yuan Mengqin, et al. Promotion of ovarian cancer cell invasion, migration and colony formation by the miR21/Wnt/CD44v6 pathway ［J］. Oncology Reports, 2019, 42(1): 91102. ［22］Li Fan, Yao Wang, Wang Weihua, et al. Carcinogenic role of KRasERK1/2 signaling in bladder cancer via inhibition of H1.2 phosphorylation at T146 ［J］. Journal of Cellular Physiology, 2019, 234(11): 2113521144.

相似文献/References:

[1]胡玲,胡健蓉,徐凤仪,等.血管内皮生长因子在子宫内膜癌中的表达及其意义[J].中国计划生育和妇产科,2011,(01):0.
　HU Ling,HU Jian-rong,XU Feng-yi,et al.[J].Chinese Journal of Family Planning & Gynecotokology,2011,(7):0.
[2]孙红敏,苑中甫.胰岛素样生长因子受体-1在子宫内膜癌组织中的表达及意义[J].中国计划生育和妇产科,2011,(02):0.
　SUN Hong-min,WAN Zhong-fu ..[J].Chinese Journal of Family Planning & Gynecotokology,2011,(7):0.
[3]田兆华,王建六.应客观评价腹膜后淋巴结切除在子宫内膜癌的治疗价值[J].中国计划生育和妇产科,2011,(03):0.
[4]陈晓丽.CD44v6、MMP-2在子宫内膜癌的表达及临床意义[J].中国计划生育和妇产科,2011,(03):0.
　CHEN Xiao-li.[J].Chinese Journal of Family Planning & Gynecotokology,2011,(7):0.
[5]梅彤,舒宽勇.CD133在子宫内膜癌中的研究进展[J].中国计划生育和妇产科,2012,(04):0.
　MEI Tong,SHU Kuan-yong* .Medical.[J].Chinese Journal of Family Planning & Gynecotokology,2012,(7):0.
[6]曹晓智,王小捷,李凤山,等.宫内膜细胞p16基因表达检测筛查子宫内膜癌的研究[J].中国计划生育和妇产科,2013,(06):0.
　Cao Xiao-zhi,Wang Xiao-jie,Li Feng-shan,et al.[J].Chinese Journal of Family Planning & Gynecotokology,2013,(7):0.
[7]廖娟,杨菊生,李越,等.磁共振成像在Ⅰ、Ⅱ期子宫内膜癌术前分期中的应用分析[J].中国计划生育和妇产科,2014,(06):0.
　LIAO Juan,YANG Ju-sheng,LI Yue,et al.[J].Chinese Journal of Family Planning & Gynecotokology,2014,(7):0.
[8]姜志欣,吴玉璘.女性人乳头瘤病毒感染及相关肿瘤[J].中国计划生育和妇产科,2014,(07):0.
[9]魏丽惠.关于子宫内膜癌筛查的思考[J].中国计划生育和妇产科,2015,(01):0.
[10]张超,蒋国庆.子宫内膜癌细胞学筛查的Meta分析[J].中国计划生育和妇产科,2015,(06):0.
　ZHANG Chao,JIANG Guo-qing,[J].Chinese Journal of Family Planning & Gynecotokology,2015,(7):0.

更新日期/Last Update: 2020-07-25