TMEM家族在乳腺癌中的研究进展

裴琴; 叶婷

doi:10.12435/j.issn.2095-5227.2023.003

TMEM家族在乳腺癌中的研究进展

doi: 10.12435/j.issn.2095-5227.2023.003

裴琴,
叶婷^,

西南医科大学附属医院医学检验部，四川泸州　646000

基金项目: 四川省科技厅-社会发展重点项目(2021YFS0226)

详细信息

作者简介:
裴琴，女，在读硕士。研究方向：分子肿瘤与肿瘤的分子诊断。Email: peiqin1221@163.com

通讯作者:
叶婷，女，博士，副教授，副主任。Email: yeting1103@163.com

中图分类号: R737.9
计量
- 文章访问数: 128
- HTML全文浏览量: 69
- PDF下载量: 9
- 被引次数: 0
出版历程
- 收稿日期: 2022-11-28
- 网络出版日期: 2023-04-14
- 刊出日期: 2023-07-28

Research advances in novelty roles of transmembrane protein family in breast cancer

PEI Qin,
YE Ting^,

Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China

More Information

Corresponding author: YE Ting. Email: yeting1103@163.com

摘要

摘要: 跨膜蛋白(transmembrane protein，TMEM)基因家族广泛参与细胞膜结构的组成，如内质网、溶酶体和高尔基体。研究发现TMEM蛋白在乳腺癌的发生发展过程中发挥重要作用，具有促癌和(或)抑癌的双重功能。TMEM不仅参与调控乳腺癌细胞的增殖、侵袭和迁移等，同时与化疗耐药有关。因此，更好地表征TMEM家族成员在乳腺癌中的表达情况、临床意义和预后价值，探索其功能可以为肿瘤的预防和治疗提供新的思路。
- 跨膜蛋白 /
- 乳腺癌 /
- 生物学行为 /
- 治疗 /
- 预后
Abstract: Transmembrane proteins (TMEM) family is widely involved in the structure of the biological membrane, including endoplasmic reticulum, lysosomes and Golgi apparatus. TMEM proteins are reported to play a pivotal role in the development of breast cancer, which have also endowed with dual functions of oncogene and/or suppressor. TMEM is not only involved in regulating the proliferation, invasion and migration of breast cancer cells, but also associated with chemotherapy resistance. Therefore, understandings of the characteristics of the expression, clinical significance and prognostic value of TMEM family members in breast cancer can provide new insights to tumor prevention and treatment.
- transmembrane protein /
- breast cancer /
- biological behavior /
- treatment /
- prognosis

HTML全文

图 1 TMEM蛋白家族的结构及基本功能

Figure 1. Structure and basic function of TMEM protein family

下载: 全尺寸图片幻灯片

图 2 TMEM蛋白家族在乳腺癌中的作用

Figure 2. The roles of TMEM protein family in breast cancer

下载: 全尺寸图片幻灯片

表 1 TMEM家族蛋白分类及功能

Table 1. Classification and function of TMEMprotein family

名称	分类	作用	参考文献
TMEM7	N-末端	肿瘤抑制因子	[23]
TMEM9	N-末端	促癌基因	[36]
TMEM16A	N-末端	促癌基因，平滑肌收缩	[18, 38, 48, 52, 54]
TMEM16F	N-末端	促癌基因	[39, 40]
TMEM17	N-末端	促癌基因	[41, 53]
TMEM25	C-末端	肿瘤抑制因子	[22, 49]
TMEM26	N-末端	肿瘤抑制因子	[29]
TMEM41B	N-末端	自噬和脂质动员	[17]
TMEM45A	C-末端	角质化，预后生物标志物	[16, 28, 30, 60]
TMEM48	N-末端	角质化	[24]
TMEM81	N-末端	参与预后	[56]
TMEM88	N-末端	促癌基因	[42, 43]
TMEM97	N-末端	肿瘤抑制因子	[20, 31, 32, 51]
TMEM100	N-末端	肿瘤抑制因子	[33, 34, 61]
TMEM116	N-末端	预后生物标志物	[25]
TMEM119	N-末端	预后生物标志物	[55]
TMEM158	C-末端	促癌基因	[44-46, 58, 59]
TMEM165	N-末端	参与高尔基糖基化	[19]
TMEM176	N-末端	逃避免疫系统	[21]
TMEM207	N-末端	预后生物标志物	[25, 26]
TMEM213	N-末端	预后生物标志物	[25, 27]

下载: 导出CSV

参考文献(62)

[1]	Sung H,Ferlay J,Siegel RL,et al. Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2021,71(3): 209-249. doi: 10.3322/caac.21660
[2]	DeSantis CE,Ma J,Gaudet MM,et al. Breast cancer statistics,2019[J]. CA Cancer J Clin,2019,69(6): 438-451. doi: 10.3322/caac.21583
[3]	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2015版)[J]. 中国癌症杂志,2015,25(9): 692-754.
[4]	沈松杰,孙强,黄欣,等. 中国女性乳腺癌筛查指南(2022年版)[J]. 中国研究型医院,2022,9(2): 6-13.
[5]	张正,张雅迪,邵佳康,等. 免疫检查点抑制剂治疗三阴性乳腺癌的研究进展[J]. 解放军医学院学报,2022,43(3): 354-359. doi: 10.3969/j.issn.2095-5227.2022.03.020
[6]	Wang YB,Zhao ZY,Jiao W,et al. PRAF2 is an oncogene acting to promote the proliferation and invasion of breast cancer cells[J]. Exp Ther Med,2022,24(6): 738. doi: 10.3892/etm.2022.11674
[7]	Harbeck N,Penault-Llorca F,Cortes J,et al. Breast cancer[J]. Nat Rev Dis Primers,2019,5: 66. doi: 10.1038/s41572-019-0111-2
[8]	Zavala VA,Bracci PM,Carethers JM,et al. Cancer health disparities in racial/ethnic minorities in the United States[J]. Br J Cancer,2021,124(2): 315-332. doi: 10.1038/s41416-020-01038-6
[9]	Chen QH,Fang JL,Shen H,et al. Roles,molecular mechanisms,and signaling pathways of TMEMs in neurological diseases[J]. Am J Transl Res,2021,13(12): 13273-13297.
[10]	Weiner C,Hecht I,Kotlyar A,et al. Association of variants in TMEM45A with keratoglobus[J]. JAMA Ophthalmol,2021,139(10): 1089-1095. doi: 10.1001/jamaophthalmol.2021.3172
[11]	Yousefi M,Lee WS,Yan BG,et al. TMEM41B and VMP1 modulate cellular lipid and energy metabolism for facilitating dengue virus infection[J]. PLoS Pathog,2022,18(8): e1010763. doi: 10.1371/journal.ppat.1010763
[12]	Wu ZH,Li C,Zhang YJ,et al. Identification of a cancer stem cells signature of head and neck squamous cell carcinoma[J]. Front Genet,2022,13: 814777. doi: 10.3389/fgene.2022.814777
[13]	Schmit K,Michiels C. TMEM proteins in cancer:a review[J]. Front Pharmacol,2018,9: 1345. doi: 10.3389/fphar.2018.01345
[14]	Marx S,Dal Maso T,Chen JW,et al. Transmembrane (TMEM) protein family members:poorly characterized even if essential for the metastatic process[J]. Semin Cancer Biol,2020,60: 96-106. doi: 10.1016/j.semcancer.2019.08.018
[15]	Entova S,Billod JM,Swiecicki JM,et al. Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds[J]. Elife,2018,7: e40889. doi: 10.7554/eLife.40889
[16]	Hayez A,Malaisse J,Roegiers E,et al. High TMEM45A expression is correlated to epidermal keratinization[J]. Exp Dermatol,2014,23(5): 339-344. doi: 10.1111/exd.12403
[17]	Moretti F,Bergman P,Dodgson S,et al. TMEM41B is a novel regulator of autophagy and lipid mobilization[J]. EMBO Rep,2018,19(9): e45889.
[18]	Thomas-Gatewood C,Neeb ZP,Bulley S,et al. TMEM16A channels generate Ca²⁺-activated Cl^- currents in cerebral artery smooth muscle cells[J]. Am J Physiol Heart Circ Physiol,2011,301(5): H1819-H1827. doi: 10.1152/ajpheart.00404.2011
[19]	Foulquier F,Amyere M,Jaeken J,et al. TMEM165 deficiency causes a congenital disorder of glycosylation[J]. Am J Hum Genet,2012,91(1): 15-26. doi: 10.1016/j.ajhg.2012.05.002
[20]	Yang K,Zeng C,Wang CC,et al. Sigma-2 receptor-a potential target for cancer/alzheimer’s disease treatment via its regulation of cholesterol homeostasis[J]. Molecules,2020,25(22): 5439. doi: 10.3390/molecules25225439
[21]	Li HX,Yang WL,Zhang MY,et al. Methylation of TMEM176A,a key ERK signaling regulator,is a novel synthetic lethality marker of ATM inhibitors in human lung cancer[J]. Epigenomics,2021,13(17): 1403-1419. doi: 10.2217/epi-2021-0217
[22]	Hrašovec S,Hauptman N,Glavač D,et al. TMEM25 is a candidate biomarker methylated and down-regulated in colorectal cancer[J]. Dis Markers,2013,34(2): 93-104. doi: 10.1155/2013/427890
[23]	Zhou XL,Popescu NC,Klein G,et al. The interferon-alpha responsive gene TMEM7 suppresses cell proliferation and is downregulated in human hepatocellular carcinoma[J]. Cancer Genet Cytogenet,2007,177(1): 6-15. doi: 10.1016/j.cancergencyto.2007.04.007
[24]	Qiao WL,Han YD,Jin W,et al. Overexpression and biological function of TMEM48 in non-small cell lung carcinoma[J]. Tumor Biol,2016,37(2): 2575-2586. doi: 10.1007/s13277-015-4014-x
[25]	Wrzesiński T,Szelag M,Cieślikowski WA,et al. Expression of pre-selected TMEMs with predicted ER localization as potential classifiers of ccRCC tumors[J]. BMC Cancer,2015,15: 518. doi: 10.1186/s12885-015-1530-4
[26]	Hano K,Hatano K,Saigo C,et al. Combination of Clptm1L and TMEM207 expression as a robust prognostic marker in oral squamous cell carcinoma[J]. Front Oral Health,2021,2: 638213. doi: 10.3389/froh.2021.638213
[27]	Zou JY,Li Z,Deng H,et al. TMEM213 as a novel prognostic and predictive biomarker for patients with lung adenocarcinoma after curative resection:a study based on bioinformatics analysis[J]. J Thorac Dis,2019,11(8): 3399-3410. doi: 10.21037/jtd.2019.08.01
[28]	Flamant L,Roegiers E,Pierre M,et al. TMEM45A is essential for hypoxia-induced chemoresistance in breast and liver cancer cells[J]. BMC Cancer,2012,12: 391. doi: 10.1186/1471-2407-12-391
[29]	Nass N,Dittmer A,Hellwig V,et al. Expression of transmembrane protein 26 (TMEM26) in breast cancer and its association with drug response[J]. Oncotarget,2016,7(25): 38408-38426. doi: 10.18632/oncotarget.9493
[30]	Lee SJ,Stewart S,Nagtegaal I,et al. Differentially expressed genes regulating the progression of ductal carcinoma in situ to invasive breast cancer[J]. Cancer Res,2012,72(17): 4574-4586. doi: 10.1158/0008-5472.CAN-12-0636
[31]	Qu TY,Zhao Y,Chen YC,et al. Down-regulated MAC30 expression inhibits breast cancer cell invasion and EMT by suppressing Wnt/β-catenin and PI3K/Akt signaling pathways[J]. Int J Clin Exp Pathol,2019,12(5): 1888-1896.
[32]	Zeng CB,Riad A,Mach RH. The biological function of Sigma-2 receptor/TMEM97 and its utility in PET imaging studies in cancer[J]. Cancers,2020,12(7): 1877. doi: 10.3390/cancers12071877
[33]	孙恃雷. BMP9通过TMEM100抑制三阴性乳腺癌细胞的作用和机制研究［D］. 重庆: 重庆医科大学, 2020.
[34]	黄佳欢,陈俊青,杨紫烟,等. PI3K/AKT/mTOR信号通路在三阴性乳腺癌中的作用及靶向治疗研究进展[J]. 肿瘤学杂志,2020,26(9): 784-790.
[35]	张哲,樊俊,刘文斌,等. 跨膜蛋白196对乳腺癌迁移及侵袭能力的影响[J]. 陆军军医大学学报,2022,44(14): 1455-1465.
[36]	彭达. TMEM9调控Wnt/β-catenin信号通路促进三阴乳腺癌细胞侵袭与迁移的机制研究［D］. 青岛: 青岛大学, 2021.
[37]	陈奕雯. ROCK1/moesin激活TMEM16A钙激活氯通道促进乳腺癌迁移侵袭的机制研究［D］. 沈阳: 中国医科大学, 2021.
[38]	郑雅乔. TMEM16A通过调控内质网应激的PERK信号通路促进乳腺癌细胞增殖机制的研究［D］. 沈阳: 中国医科大学, 2022.
[39]	樊璐,王慧,肖庆桓. 跨膜蛋白16F对乳腺癌细胞增殖及迁移的影响[J]. 中国医科大学学报,2019,48(2): 124-127.
[40]	张璐. TMEM16F通过内质网应激相关的PERK通路促进乳腺癌细胞的增殖和迁移［D］. 沈阳: 中国医科大学, 2021.
[41]	宋奎园. TMEM17通过AKT/GSK3β信号通路促进乳腺癌的恶性进展［D］. 沈阳: 中国医科大学, 2018.
[42]	Yu XM,Zhang XP,Zhang Y,et al. Cytosolic TMEM88 promotes triple-negative breast cancer by interacting with Dvl[J]. Oncotarget,2015,6(28): 25034-25045. doi: 10.18632/oncotarget.4379
[43]	Lee HJ,Finkelstein D,Li XF,et al. Identification of transmembrane protein 88 (TMEM88) as a dishevelled-binding protein[J]. J Biol Chem,2010,285(53): 41549-41556. doi: 10.1074/jbc.M110.193383
[44]	Tong JC,Li HR,Hu Y,et al. TMEM158 regulates the canonical and non-canonical pathways of TGF-β to mediate EMT in triple-negative breast cancer[J]. J Cancer,2022,13(8): 2694-2704. doi: 10.7150/jca.65822
[45]	童佳慈. 跨膜蛋白TMEM158通过介导EMT过程促进三阴型乳腺癌发生及发展和其分子机制研究［D］. 大连: 大连医科大学, 2022.
[46]	朱雪峰,刘彦魁,张亚. TMEM158、CTEN在乳腺癌组织表达水平及意义[J]. 中南医学科学杂志,2020,48(6): 604-607.
[47]	Łukasiewicz S,Czeczelewski M,Forma A,et al. Breast cancer-epidemiology,risk factors,classification,prognostic markers,and current treatment strategies-an updated review[J]. Cancers (Basel),2021,13(17): 4287. doi: 10.3390/cancers13174287
[48]	宋寒宾. 乳腺癌他莫昔芬耐药细胞中钙激活氯通道TMEM16A下调激活自噬的机制研究［D］. 沈阳: 中国医科大学, 2021.
[49]	Li Y,Wang YY,Wang HF,et al. Effects of lncRNA RP11-770J1.3 and TMEM25 expression on paclitaxel resistance in human breast cancer cells[J]. Zhejiang Da Xue Xue Bao Yi Xue Ban,2017,46(4): 364-370.
[50]	门欣. NPYIR和TMEM47调控乳腺癌他莫昔芬和紫杉醇多药耐药的代谢通路研究与分析［D］. 西安: 西北大学, 2021.
[51]	Zhu HF,Su ZJ,Ning J,et al. Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer[J]. Cell Death Dis,2021,12(10): 912. doi: 10.1038/s41419-021-04211-8
[52]	柯永莉,李黎,寇晓梅,等. 乳腺癌组织miR-381和跨膜蛋白16A表达与临床病理特征及预后的关系[J]. 中华实用诊断与治疗杂志,2022,36(7): 714-718.
[53]	Zhao Y,Song KY,Zhang Y,et al. TMEM17 promotes malignant progression of breast cancer via AKT/GSK3β signaling[J]. Cancer Manag Res,2018,10: 2419-2428. doi: 10.2147/CMAR.S168723
[54]	Crottès D,Jan LY. The multifaceted role of TMEM16A in cancer[J]. Cell Calcium,2019,82: 102050. doi: 10.1016/j.ceca.2019.06.004
[55]	Yang B,Wang FL,Zheng G. Transmembrane protein TMEM119 facilitates the stemness of breast cancer cells by activating Wnt/β-catenin pathway[J]. Bioengineered,2021,12(1): 4856-4867. doi: 10.1080/21655979.2021.1960464
[56]	张虎,杜欣娜,庄莹,等. 乳腺癌中跨膜蛋白81基因高表达不利于患者预后[J]. 中国临床解剖学杂志,2018,36(5): 586-589.
[57]	李健,王颜. TMEM65表达对乳腺癌患者预后的影响[J]. 山东第一医科大学(山东省医学科学院)学报,2022,43(3): 198-204.
[58]	Wang LC,Wang WH,Zeng SP,et al. Construction and validation of a 6-gene nomogram discriminating lung metastasis risk of breast cancer patients[J]. PLoS One,2020,15(12): e0244693. doi: 10.1371/journal.pone.0244693
[59]	翁剑华,廖瑜玲,许素真. TMEM158在乳腺癌中的表达及与临床特征及预后的相关性[J]. 热带医学杂志,2019,19(1): 72-75. doi: 10.3969/j.issn.1672-3619.2019.01.018
[60]	Schmit K,Chen JW,Ayama-Canden S,et al. Characterization of the role of TMEM45A in cancer cell sensitivity to cisplatin[J]. Cell Death Dis,2019,10(12): 919. doi: 10.1038/s41419-019-2088-x
[61]	卢晨欣. 雷公藤红素上调TMEM100蛋白抑制乳腺癌细胞MDA-MB-231转移［D］. 南充: 西华师范大学, 2017.
[62]	张哲. 基于生物信息学分析TMEM196和NR3C2对乳腺癌患者预后的影响及功能验证［D］. 重庆: 中国人民解放军陆军军医大学, 2022.