CD147相关复合物在肿瘤功能中的研究进展

doi:10.14088/j.cnki.issn0439-8114.2021.10.002

摘要/Abstract

摘要： CD147也称为Basigin或细胞外基质金属蛋白酶诱导剂（EMMPRIN）,属于免疫球蛋白超家族（IgSF）。CD147形成的复合物可通过多种途径影响肿瘤细胞的增殖、黏附、侵袭、转移和能量代谢。CD147在恶性肿瘤中高度表达,已被作为多种肿瘤预后评估的标志物和潜在的治疗靶标,在利用CD147定向单克隆抗体对肿瘤进行治疗方面已经取得了一些进展。主要对CD147复合物在肿瘤中的功能以及CD147作为潜在治疗靶标的用途进行综述。

关键词: CD147相关复合物, 侵袭转移, 肿瘤代谢, 靶向治疗

Abstract: CD147 is also known as Basigin or extracellular matrix metalloproteinase inducer （EMMPRIN）, which belongs to the immunoglobulin superfamily （IgSF）. The complex formed by CD147 can affect the proliferation, adhesion, invasion, metastasis and energy metabolism of tumor cells through a variety of ways. CD147 is highly expressed in malignant tumors, it has been used as a marker for prognostic evaluation of multiple tumors and a potential therapeutic target. At present, some progress has been made in the use of CD147-directed antibodies to treat tumors. This article mainly reviews the function of CD147 complex in tumors and the use of CD147 as a potential therapeutic target.

Key words: CD147-related complexes, invasion and metastasis, tumor metabolism, targeted therapy

中图分类号:

R730

刘静, 徐冰红, 王丽, 焦文豪, 张维, 董敏敏, 严汉池. CD147相关复合物在肿瘤功能中的研究进展[J]. 湖北农业科学, 2021, 60(10): 10-14.

LIU Jing, XU Bing-hong, WANG Li, JIAO Wen-hao, ZHANG Wei, DONG Min-min, YAN Han-chi. Research progress of CD147-related complexes in tumor function[J]. HUBEI AGRICULTURAL SCIENCES, 2021, 60(10): 10-14.

参考文献

[1] KUMAR D, VETRIVEL U, PARAMESWARAN S, et al.Structural insights on druggable hotspots in CD147: A bull's eye view[J]. Life sciences, 2019,224:76-87.
[2] MIKIKO A, KAORI K, MAKOTO H, et al.Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with fibroblasts[J]. International journal of oncology, 2017, 50(6):2229-2235.
[3] WU B, CUI J, YANG X M, et al.Cytoplasmic fragment of CD147 generated by regulated intramembrane proteolysis contributes to HCC by promoting autophagy[J]. Cell death & disease, 2017, 8(7):e2925.
[4] ALBRECHTSEN R, ALBRECHTSEN N J, GNOSA S P, et al.Identification of ADAM12 as a novel basigin sheddase[J]. International journal of molecular sciences, 2019, 20(8):1957.
[5] LANDRAS A, DE MOURA C R, JOUENNE F, et al. CD147 is a promising target of tumor progression and a prognostic biomarker[J]. Cancers, 2019, 11(11):1803.
[6] DING P, ZHANG X, JIN S, et al.CD147 functions as the signaling receptor for extracellular divalent copper in hepatocellular carcinoma cells[J]. Oncotarget, 2017, 8(31):51151-51163.
[7] AOKI M, KOGA K, MIYAZAKI M, et al.CD73 complexes with emmprin to regulate MMP-2 production from co-cultured sarcoma cells and fibroblasts[J]. BMC cancer, 2019, 19(1):912.
[8] XU X, PAN W, KANG L, et al.Association of annexin A2 with cancer development (review)[J]. Oncology reports, 2015, 33(5): 2121-2128.
[9] LUO Z, ZHANG X, ZENG W, et al.TRAF6 regulates melanoma invasion and metastasis through ubiquitination of basigin[J]. Oncotarget, 2016, 7(6):7179-7192.
[10] LI J, HUANG W, LIN P, et al.N-linked glycosylation at Asn152 on CD147 affects protein folding and stability:Promoting tumour metastasis in hepatocellular carcinoma[J].Scientific reports,2016, 6(1):35210.
[11] CUI J, HUANG W, WU B, et al.N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis[J]. The journal of pathology, 2018, 245(1):41-52.
[12] JIN J, WANG S, CUI J, et al.Hypo-phosphorylated CD147 promotes migration and invasion of hepatocellular carcinoma cells and predicts a poor prognosis[J]. Cellular oncology, 2019,42(4):537-554.
[13] ZHANG X, HUANG Z N, GUO Y Y,et al.The phosphorylation of CD147 by Fyn plays a critical role for melanoma cells growth and metastasis[J]. Oncogene,2020,39:4183-4197.
[14] KNUTTI N, KUEPPER M, FRIEDRICH K, et al.Soluble extracellular matrix metalloproteinase inducer (EMMPRIN, EMN) regulates cancer-related cellular functions by homotypic interactions with surface CD147[J]. FEBS journal, 2015, 282(21):4187-4200.
[15] QIN H, RASUL A, LI X, et al.CD147-induced cell proliferation is associated with Smad4 signal inhibition[J]. Experimental cell research, 2017, 358(2):279-289.
[16] FEI F, LI X, XU L, et al.CD147-CD98hc complex contributes to poor prognosis of non-small cell lung cancer patients through promoting cell proliferation via the PI3K/Akt signaling pathway[J]. Annals of surgical oncology, 2014, 21(13):4359-4368.
[17] PENG J M, JIANG H T, GUO J N, et al.CD147 expression is associated with tumor proliferation in bladder cancer via GSDMD[J]. BioMed research international, 2020,2020:7638975.
[18] ZHU D, WANG Z, ZHAO J J, et al.The cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells.[J]. Nature medicine, 2015, 21(6):572-580.
[19] LI L, XIAOXIA D, FENG P, et al.Integrin β1 regulates the invasion and radioresistance of laryngeal cancer cells by targeting CD147[J]. Cancer cell international, 2018, 18(1):80.
[20] WANG S, CUI H, LIU Y, et al.CD147 promotes Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells.[J]. Oncotarget, 2015, 6(1):243-257.
[21] DELYON J, KHAYATI F, DJAAFRI I, et al.EMMPRIN regulates β1 integrin-mediated adhesion through Kindlin-3 in human melanoma cells[J]. Experimental dermatology, 2015, 24(6):443-448.
[22] CUI H, WANG S, MIAO J, et al.CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling[J]. Oncotarget, 2016, 7(5):5613-5629.
[23] LI F, ZHANG J, GUO J, et al.RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression[J]. Acta biochimica et biophysica sinica, 2018, 50(7):676-684.
[24] TANG Y, NAKADA M T, RAFFERTY P, et al.Regulation of vascular endothelial growth factor expression by EMMPRIN via the PI3K-Akt signaling pathway[J]. Molecular cancer research, 2006, 4(6):371-377.
[25] KHAYATI F, PEREZCANO L, MAOUCHE K, et al.EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF[J]. Oncotarget, 2015, 6(12):9766-9780.
[26] PAYEN V L, MINA E, VAN HEE V F, et al. Monocarboxylate transporters in cancer[J]. Molecular metabolism, 2020,33: 48-66.
[27] FOREROQUINTERO L S, AMES S, SCHNEIDER H, et al.Membrane-anchored carbonic anhydrase IV interacts with monocarboxylate transporters via their chaperones CD147 and GP70[J]. Journal of biological chemistry, 2019, 294(2):593-607.
[28] AMES S, ANDRING J T, MCKENNA R, et al.CAIX forms a transport metabolon with monocarboxylate transporters in human breast cancer cells[J]. Oncogene, 2020, 39(8):1710-1723.
[29] MARCHIQ I, ALBRENGUES J, GRANJA S, et al.Knock out of the BASIGIN/CD147 chaperone of lactate/H+ symporters disproves its pro-tumour action via extracellular matrix metalloproteases (MMPs) induction[J]. Oncotarget, 2015, 6(28):24636-24648.
[30] SU J, GAO T, JIANG M, et al.CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma[J]. Oncotarget, 2016, 7(40):64778-64784.
[31] LI J, HUANG Q, LONG X, et al.CD147 reprograms fatty acid metabolism in hepatocellular carcinoma cells through Akt/mTOR/SREBP1c and P38/PPARα pathways[J]. Journal of hepatology,2015, 63(6):1378-1389.
[32] LI H, JIANG C, WU D, et al.The prognostic and clinicopathologic characteristics of CD147 and esophagus cancer:A meta-analysis[J]. PloS one, 2017, 12(7):e0180271.
[33] TOOLE B P.The CD147-HYALURONAN axis in cancer[J]. Anatomical record-advances in integrative anatomy and evolutionary biology, 2020,303(6):1573-1583.
[34] ZHOU S, LIAO L, CHEN C, et al.CD147 mediates chemoresistance in breast cancer via ABCG2 by affecting its cellular localization and dimerization[J]. Cancer letters, 2013, 337(2): 285-292.
[35] KUANG Y, WANG S, TANG L, et al.Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity[J]. Oncology letters, 2018, 15(5):1792-1074.
[36] WANG Y, YUAN L, YANG X, et al.A chimeric antibody targeting CD147 inhibits hepatocellular carcinoma cell motility via FAK-PI3K-Akt-Girdin signaling pathway[J]. Clinical & experimental metastasis, 2015, 32(1):39-53.
[37] FAN X Y, HE D, SHENG C B, et al.Therapeutic anti-CD147 antibody sensitizes cells to chemoradiotherapy via targeting pancreatic cancer stem cells[J]. American journal of translational research, 2019, 11(6):3543.
[38] WANG S H, LIU C, LIU X J, et al. Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines[J/OL]. Tumor biology,https://doi.org/10.1177/1010428317718192, 2017-10-15.
[39] FU Z,WANG L,CUI H, et al.A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells[J]. Oncotarget,2016, 7(8):9429-9447.
[40] SPINELLO I, SAULLE E, QUARANTA M T, et al.The small-molecule compound AC-73 targeting CD147 inhibits leukemic cell proliferation, induces autophagy and increases the chemotherapeutic sensitivity of acute myeloid leukemia cells[J]. Haematologica, 2018, 104(5):973-985.