富亮氨酸重复序列(LRR)存在于多种蛋白质中,介导多种蛋白与蛋白之间的相互作用。近年来一些研究发现:LRRC超家族成员LRRC4、LRRC3B和LG11在多种肿瘤组织表达缺失或显著降低,并具有抑癌基因的功能;而另外一些LRRC超家族成员LGR4和LGR5在肿瘤中高表达,表现出原癌基因的作用。以上研究提示它们可能成为肿瘤诊断和治疗的新靶点。本文就LRRC超家族成员在肿瘤的研究进展进行回顾性综述。 The leucine rich repeat sequence (LRR) domains are known to mediate protein-protein interactions. In recent years, some studies have found that members of the LRRC super family (for example LRRC4, LRRC3B and LG11) were absent or significantly down-expressed in a variety of tumor tissue, and have the potential of suppressing tumorigenesis and tumor cell proliferation. LGR4 and LGR5 are up-expression in tumor, and show the function of proto-oncogene. These findings suggested that members of the LRRC super family may become the new target for diagnosis and treatment of tumor. In the present review we summarize the current literature about LRRC super family in the cancer.
史婧怡,陈妍珂. LRRC超家族成员在肿瘤的研究进展 The Progress of Research on LRRC Super Family Members in Cancer[J]. 世界肿瘤研究, 2018, 08(02): 81-85. https://doi.org/10.12677/WJCR.2018.82013
参考文献ReferencesTakahashi, N., Takahashi, Y. and Putnam, F.W. (1985) Periodicity of Leucine and Tandem Repetition of a 24-Amino Acid Segment in the Primary Structure of Leucine-Rich Alpha 2-Glycoprotein of Human Serum. Proceedings of the National Academy of Sciences of the United States of America, 82, 1906-1910. https://doi.org/10.1073/pnas.82.7.1906李丹, 李桂源. 富亮氨酸重复超家族成员与脑瘤的研究进展[J]. 国际病理科学与临床杂志, 2006, 26(6): 466-468Kobe, B. and Deisenhofer, J. (1993) Crystal Structure of Porcine Ribonuclease Inhibitor, a Protein with Leucine-Rich Repeats. Nature, 366, 751-756. https://doi.org/10.1038/366751a0Kobe, B. and Deisenhofer, J.A. (1995) Structural Basis of the Interactions between Leucine-Rich Repeats and Protein Ligands. Nature, 374, 183-186. https://doi.org/10.1038/374183a0Kobe, B. and Kajava, A.V. (2001) The Leucine-Rich Repeat as a Protein Recognition Motif. Current Opinion in Structural Biology, 11, 725-732. https://doi.org/10.1016/S0959-440X(01)00266-4Gunduz, M., Ouchida, M., Fukushima, K., et al. (2002) Allelic Loss and Reduced Expression of the ING3, a Candidate Tumor Suppressor Gene at 7q31, in Human Head and Neck Cancers. Oncogene, 21, 4462-4470.
https://doi.org/10.1038/sj.onc.1205540Tan, G., Xiao, J., Tian, Y., et al. (2002) Microsatellite Analyses of Loci at 7q31.3-q36 Reveal a Minimum of Two Common Regions of Deletion in Nasopharyngeal Carcinoma. Otolaryngology—Head and Neck Surgery, 126, 296-300. https://doi.org/10.1067/mhn.2002.123046Haddad, R., Vincent, J.B., Gryfe, R., et al. (2004) Chromosome 7q31 Allelic Imbalance and Somatic Mutations of RAY1/ST7 Gene in Colorectal Cancer. Cancer Letters, 203, 87-90. https://doi.org/10.1016/j.canlet.2003.08.003Kawana, Y., Ichikawa, T., Suzaki, H., et al. (2002) Loss of Heterozygosity at 7q31.1 and 12p13-12 in Advanced Prostate Cancer. Prostate, 53, 60-64. https://doi.org/10.1002/pros.10131Zenklusen, J.C., Conti, C.J. and Green, E.D. (2001) Mutational and Functional Analyses Reveal that ST7 Is a Highly Conserved Tumor-Suppressor Gene on Human Chromosome 7q31. Nature Genetics, 27, 392-398.
https://doi.org/10.1038/86891Chernova, O.B., Somerville, R.P. and Cowell, J.K. (1998) A Novel Gene, LGI1, from 10q24 Is Rearranged and Downregulated in Malignant Brain Tumors. Oncogene, 17, 2873-2881. https://doi.org/10.1038/sj.onc.1202481王洁如, 钱骏, 董利, 等. 富亮氨酸重复超家族新成员LRRC4的克隆与在脑瘤中的表达分析[J]. 生物化学与生物物理进展, 2002, 29(2): 233-239.Zhang, Q., Wang, J., Fan, S., et al. (2005) Expression and Functional Characterization of LRRC4, a Novel Brain-Specific Member of the LRR Superfamily. FEBS Letters, 579, 3674-3682.Wang, J.R., Li, X.L., Fan, S.Q., et al. (2003) Expression of LRRC4 Has the Potential to Decrease the Growth Rate and Tumorigenesis of Glioblastoma Cell Line U251. Chinese Journal of Cancer, 22, 897-902.武明花, 唐运莲, 李小玲, 曹利, 李桂源. LRRC4通过LRR结构域抑制脑胶质母细胞瘤U251细胞的生长和侵袭[J]. 中国生物化学与分子生物学报, 2007, 23(8): 617-624.陈琼, 武明花, 周艳宏, 唐运莲, 黄琛, 李小玲, 李桂源. LRRC4通过SDF-1α/CXCR4生物学轴抑制脑胶质瘤细胞侵袭迁移能力[J]. 中南大学学报(医学版), 2007, 32(5): 735-741.Krex, D., Hauses, M., Appeh, H., et al. (2002) Physical and Functional Characterization of the Human LGll Gene and Its Possible Role in Glioma Development. Acta Neuropathologica, 103, 255-266.
https://doi.org/10.1007/s004010100463Kunapuli, P., Chitta, K.S. and Cowell, J.K. (2003) Suppression of the Cell Proli-feration and Invasion Phenotypes in Glioma Cells by the LGll Gene. Oncogene, 22, 3985-3991. https://doi.org/10.1038/sj.onc.1206584Richardson, A.L., Wang, Z.C., De Nicolo, A., et al. (2006) X Chromosomal Ab-normalities in Basal-Like Human Breast Cancer. Cancer Cell, 9, 121-132. https://doi.org/10.1016/j.ccr.2006.01.013Sun, L., Hui, A.M., Su, Q., et al. (2006) Neuronal and Glioma-Derived Stem Cell Factor Induces Angiogenesis within the Brain. Cancer Cell, 9, 287-300. https://doi.org/10.1016/j.ccr.2006.03.003Bianchini, M., Levy, E., Zucchini, C., et al. (2006) Comparative Study of Gene Expression by cDNA Microarray in Human Colorectal Cancer Tissues and Normal Mucosa. International Journal of Oncology, 29, 83-94.Lapointe, J., Li, C., Higgins, J.P., et al. (2004) Gene Expression Profiling Identifies Clinically Relevant Subtypes of Prostate Cancer. Proceedings of the National Academy of Sciences of the United States of America, 101, 811-816.
https://doi.org/10.1073/pnas.0304146101Chen, X., Leung, S.Y., Yuen, S.T., et al. (2003) Variation in Gene Expression Patterns in Human Gastric Cancers. Molecular Biology of the Cell, 14, 3208-3230.阚亮, 张萌, 何平. LRRC3B在非小细胞肺癌中表达下调及其与高TNM分期、淋巴结转移的相关性[J]. 中国医学前沿杂志(电子版), 2016, 8(5): 131-135.Wang, Y., Peng, Y., Zhou, Y., et al. (2014) The Clinical Value of LRRC3B Gene Expression and Promoter Hypermethylation in Breast Carci-nomas. Cell Biochemistry and Biophysics, 70, 1035-1041.
https://doi.org/10.1007/s12013-014-0018-1张祖萍, 武明花, 唐海林, 王蓉, 李丹, 李小玲, 李桂源. 5-Aza-CdR对胶质瘤细胞生长及LRRC4基因异常甲基化的影响[J]. 生物化学与生物物理进展, 2009, 36(7): 904-909.Zhang, J., Li, Q., Zhang, S., Xu, Q. and Wang, T. (2016) Lgr4 Promotes Prostate Tumorigenesis through the Jmjd2a/AR Signaling Pathway. Experi-mental Cell Research, 349, 77-84.Fukuma, M., Tanese, K., Effendi, K., Yamazaki, K., Masugi, Y., Suda, M., et al. (2013) Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 Regulates Epithelial Cell Phenotype and Survival of Hepatocellular Carcinoma Cells. Experimental Cell Research, 319, 113-121.Yamanoi, K., Fukuma, M., Uchida, H., Kushima, R., Yamazaki, K., Katai, H., et al. (2013) Overexpression of Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 in Gastric Cancer. Pathology International, 63, 13-19.Tanese, K., Fukuma, M., Yamada, T., Mori, T., Yoshikawa, T., Watanabe, W., et al. (2008) G-Protein-Coupled Receptor GPR49 Is Up-Regulated in Basal Cell Carcinoma and Promotes Cell Proliferation and Tumor Formation. The American Journal of Pathology, 173, 835-843.McClanahan, T., Koseoglu, S., Smith, K., Grein, J., Gustafson, E., Black, S., et al. (2006) Identification of Overexpression of Orphan G Protein-Coupled Receptor GPR49 in Human Colon and Ovarian Primary Tumors. Cancer Biology & Therapy, 5, 419-426.