PLEKHA蛋白家族在恶性肿瘤中的研究进展
Research Progress of PLEKHA Protein Family in Cancer
DOI: 10.12677/ACM.2023.1351120, PDF,   
作者: 赵改霞, 沈国双*:青海大学附属医院乳腺疾病诊疗中心,青海 西宁
关键词: PLEKHA蛋白家族黑色素瘤乳腺癌结肠癌PLEKHA Protein Family Melanoma Breast Cancer Colon Cancer
摘要: PLEKHA是含有pleckstrin同源(PH)结构域的蛋白家族,PH结构域是约100个氨基酸的蛋白质模块,其存在于参与磷酸肌醇代谢、信号传导和细胞骨架组织的多种蛋白质中,PLEKHA蛋白家族包含三个独立的亚家族。而PLEKHA4/5/6/7与多种人类肿瘤关系密切,遂本文对PLEKHA蛋白家族与恶性肿瘤的关系做一综述,以明确PLEKHA蛋白家族在恶性肿瘤中的作用。
Abstract: PLEKHA is a family of proteins containing the pleckstrin homologous (PH) domain. The PH domain is a protein module of about 100 amino acids that is present in a variety of proteins involved in phos-phoinositol metabolism, signaling, and cytoskeletal organization. The PLEKHA protein family con-tains three separate subfamilies. PLEKHA4/5/6/7 is closely related to a variety of human tumors, so this paper reviews the relationship between PLEKHA protein family and malignant tumors to clarify the role of PLEKHA protein family in cancer.
文章引用:赵改霞, 沈国双. PLEKHA蛋白家族在恶性肿瘤中的研究进展[J]. 临床医学进展, 2023, 13(5): 7999-8007. https://doi.org/10.12677/ACM.2023.1351120

参考文献

[1] Dowler, S., Currie, R.A., Campbell, D.G., et al. (2000) Identification of Pleckstrin-Homology-Domain-Containing Pro-teins with Novel Phosphoinositide-Binding Specificities. Biochemical Journal, 351, 19-31. [Google Scholar] [CrossRef
[2] Maffucci, T. and Falasca, M. (2001) Specificity in Pleckstrin Homology (PH) Domain Membrane Targeting: A Role for a Phosphoinositide-Protein Cooperative Mechanism. FEBS Letters, 506, 173-179. [Google Scholar] [CrossRef
[3] Kourtidis, A., Dighera, B., Risner, A., Hackemack, R. and Nikolaidis, N. (2022) Origin and Evolution of the Multifaceted Adherens Junction Component Plekha7. Frontiers in Cell and Developmental Biology, 10, Article ID: 856975. [Google Scholar] [CrossRef] [PubMed]
[4] Sluysmans, S., Méan, I., Xiao, T., et al. (2021) PLEKHA5, PLEKHA6, and PLEKHA7 Bind to PDZD11 to Target the Menkes ATPase ATP7A to the Cell Periphery and Regulate Copper Homeostasis. Molecular Biology of the Cell, 32, ar34. [Google Scholar] [CrossRef
[5] Troyanovsky, R.B., Sergeeva, A.P., Indra, I., et al. (2021) Sorting of Cadherin-Catenin-Associated Proteins into Individual Clusters. Proceedings of the National Academy of Sciences of the United States of America, 118, e2105550118. [Google Scholar] [CrossRef] [PubMed]
[6] Ostrom, Q.T., Gittleman, H., Stetson, L., Virk, S.M. and Barn-holtz-Sloan, J.S. (2015) Epidemiology of Gliomas. Cancer Treatment Research, 163, 1-14. [Google Scholar] [CrossRef] [PubMed]
[7] Zhang, W., Li, L., Bian, P.P., Luo, Q.P. and Xiong, Z.T. (2023) PLEKHA4 Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Glioma. BioMed Research International, 2023, Article ID: 4504474. [Google Scholar] [CrossRef] [PubMed]
[8] Cancer Genome Atlas Network (2015) Genomic Classification of Cu-taneous Melanoma. Cell, 161, 1681-1696. [Google Scholar] [CrossRef] [PubMed]
[9] Garbe, C. and Leiter, U. (2009) Melanoma Epidemiology and Trends. Clinics in Dermatology, 27, 3-9. [Google Scholar] [CrossRef] [PubMed]
[10] Miller, A.J. and Mihm, M.C. (2006) Melanoma. The New England Journal of Medicine, 355, 51-65. [Google Scholar] [CrossRef
[11] Zhan, T., Rindtorff, N. and Boutros, M. (2017) Wnt Signaling in Cancer. Oncogene, 36, 1461-1473. [Google Scholar] [CrossRef] [PubMed]
[12] Shami Shah, A., Cao, X., White, A.C. and Baskin, J.M. (2021) PLEKHA4 Promotes Wnt/β-Catenin Signaling-Mediated G1-S Transition and Proliferation in Melanoma. Cancer Re-search, 81, 2029-2043. [Google Scholar] [CrossRef
[13] Nusse, R. and Clevers, H. (2017) Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell, 169, 985-999. [Google Scholar] [CrossRef] [PubMed]
[14] Yamada, K., Nomura, N., Yamano, A., Yamada, Y. and Wakamatsu, N. (2012) Identification and Characterization of Splicing Variants of PLEKHA5 (Plekha5) during Brain Development. Gene, 492, 270-275. [Google Scholar] [CrossRef] [PubMed]
[15] Nieder, C., Adam, M. and Astner, S.T. (2008) Disease Presenta-tion and Outcome in Young Patients (<40 Years) with Brain Metastases from Malignant Melanoma. AntiCancer Re-search, 28, 1325-1327.
[16] Simonsen, T.G., Gaustad, J.V. and Rofstad, E.K. (2015) Intertumor Heterogeneity in Vas-cularity and Invasiveness of Artificial Melanoma Brain Metastases. Journal of Experimental & Clinical Cancer Research, 34, 150. [Google Scholar] [CrossRef] [PubMed]
[17] Simonsen, T.G., Gaustad, J.V. and Rofstad, E.K. (2016) Intracra-nial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma. Translational Oncology, 9, 211-218. [Google Scholar] [CrossRef] [PubMed]
[18] Gottschalk, J., Döpel, S.H., Schulz, J., Fuchs, M. and Martin, H. (1987) Bedeutung der Immunhistochemie für die Neuroonkologie. V. Mitteilung. Keratin als Marker einer epithelialen Differenzierung primärer und sekundärer intrakranieller und intraspinaler Tumoren [Significance of Immunohistochemis-try in Neuro-Oncology. V. Keratin as a Marker for Epithelial Differentiation of Primary and Secondary Intracranial and Intraspinal Tumors]. Zentralblatt für allgemeine Pathologie und Pathologische Anatomie, 133, 133-145.
[19] Schouten, L.J., Rutten, J., Huveneers, H.A. and Twijnstra, A. (2002) Incidence of Brain Metastases in a Cohort of Patients with Carcinoma of the Breast, Colon, Kidney, and Lung and Melanoma. Cancer, 94, 2698-2705. [Google Scholar] [CrossRef] [PubMed]
[20] Sandru, A., Voinea, S., Panaitescu, E. and Blidaru, A. (2014) Survival Rates of Patients with Metastatic Malignant Melanoma. Journal of Medicine and Life, 7, 572-576. [Google Scholar] [CrossRef] [PubMed]
[21] Jilaveanu, L.B., Parisi, F., Barr, M.L., et al. (2015) PLEKHA5 as a Bi-omarker and Potential Mediator of Melanoma Brain Metastasis. Clinical Cancer Research, 21, 2138-2147. [Google Scholar] [CrossRef
[22] Fazakas, C., Wilhelm, I., Nagyoszi, P., et al. (2011) Trans-migration of Melanoma Cells through the Blood-Brain Barrier: Role of Endothelial Tight Junctions and Melano-ma-Released Serine Proteases. PLOS ONE, 6, e20758. [Google Scholar] [CrossRef] [PubMed]
[23] Eisele, S.C., Gill, C.M., Shankar, G.M. and Brastianos, P.K. (2015) PLEKHA5: A Key to Unlock the Blood-Brain Barrier? Clinical Cancer Research, 21, 1978-1980. [Google Scholar] [CrossRef
[24] Zhang, H., Zhu, H., Deng, G., et al. (2020) PLEKHA5 Regulates Tumor Growth in Metastatic Melanoma. Cancer, 126, 1016-1030. [Google Scholar] [CrossRef] [PubMed]
[25] Zou, Y. and Zhong, W. (2012) A Likely Role for a Novel PH-Domain Containing Protein, PEPP2, in Connecting Membrane and Cytoskeleton. Biocell, 36, 127-132. [Google Scholar] [CrossRef
[26] Chen, G., Chakravarti, N., Aardalen, K., et al. (2014) Molecular Profiling of Patient-Matched Brain and Extracranial Melanoma Metastases Implicates the PI3K Pathway as a Therapeutic Target. Clinical Cancer Research, 20, 5537-5546. [Google Scholar] [CrossRef
[27] Niessner, H., Schmitz, J., Tabatabai, G., et al. (2016) PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases in Vitro and in Vivo [Published Correction Appears in Clin Cancer Res. 2017 Mar 1; 23(5): 1361]. Clinical Cancer Research, 22, 5818-5828. [Google Scholar] [CrossRef
[28] Song, W., Zhang, H., Yang, F., et al. (2023) Single Cell Profiling of γδ Hepatosplenic T-Cell Lymphoma Unravels Tumor Cell Heterogeneity Associated with Disease Progres-sion. Cellular Oncology (Dordrecht), 46, 211-226. [Google Scholar] [CrossRef] [PubMed]
[29] Jiang, F. and Shen, X. (2019) Current Prevalence Status of Gas-tric Cancer and Recent Studies on the Roles of Circular RNAs and Methods Used to Investigate Circular RNAs. Cellular & Molecular Biology Letters, 24, 53. [Google Scholar] [CrossRef] [PubMed]
[30] Quail, D.F. and Joyce, J.A. (2017) The Microenvironmental Landscape of Brain Tumors. Cancer Cell, 31, 326-341. [Google Scholar] [CrossRef] [PubMed]
[31] Dapash, M., Hou, D., Castro, B., Lee-Chang, C. and Lesniak, M.S. (2021) The Interplay between Glioblastoma and Its Microenvironment. Cells, 10, 2257. [Google Scholar] [CrossRef] [PubMed]
[32] 王慧霞. 胃癌外泌体中的PLEKHA4通过促进巨噬细胞向M2表型极化以促进胃癌的进展[C]//第十四届全国免疫学学术大会论文摘要汇编. 2021: 214.
[33] Chen, Y., Zhou, Q., Wang, H., et al. (2020) Predicting Peritoneal Dissemination of Gastric Cancer in the Era of Precision Medicine: Molecu-lar Characterization and Biomarkers. Cancers (Basel), 12, Article No. 2236. [Google Scholar] [CrossRef] [PubMed]
[34] Yashiro, M. and Hirakawa, K. (2010) Cancer-Stromal Interactions in Scirrhous Gastric Carcinoma. Cancer Microenvironment, 3, 127-135. [Google Scholar] [CrossRef] [PubMed]
[35] Ikeguchi, M., Miyake, T., Matsunaga, T., et al. (2009) Recent Results of Therapy for Scirrhous Gastric Cancer. Surgery Today, 39, 290-294. [Google Scholar] [CrossRef] [PubMed]
[36] Otsuji, E., Kuriu, Y., Okamoto, K., et al. (2004) Outcome of Sur-gical Treatment for Patients with Scirrhous Carcinoma of the Stomach. The American Journal of Surgery, 188, 327-332. [Google Scholar] [CrossRef] [PubMed]
[37] Hattori, Y., Itoh, H., Uchino, S., et al. (1996) Immunohisto-chemical Detection of K-sam Protein in Stomach Cancer. Clinical Cancer Research, 2, 1373-1381.
[38] Kuniyasu, H., Yasui, W., Kitadai, Y., Yokozaki, H., Ito, H. and Tahara, E. (1992) Frequent Amplification of the c-met Gene in Scir-rhous Type Stomach Cancer. Biochemical and Biophysical Research Communications, 189, 227-232. [Google Scholar] [CrossRef
[39] Toiyama, Y., Yasuda, H., Saigusa, S., et al. (2012) Co-Expression of Hepatocyte Growth Factor and c-Met Predicts Peritoneal Dissemination Established by Autocrine Hepatocyte Growth Factor/c-Met Signaling in Gastric Cancer. International Journal of Cancer, 130, 2912-2921. [Google Scholar] [CrossRef] [PubMed]
[40] Trusolino, L., Bertotti, A. and Comoglio, P.M. (2010) MET Signalling: Principles and Functions in Development, Organ Regeneration and Cancer. Nature Reviews Molecular Cell Biology, 11, 834-848. [Google Scholar] [CrossRef] [PubMed]
[41] Nagamura, Y., Miyazaki, M., Nagano, Y., et al. (2021) PLEKHA5 Regulates the Survival and Peritoneal Dissemination of Diffuse-Type Gastric Carcinoma Cells with Met Gene Amplifica-tion. Oncogenesis, 10, Article No. 25. [Google Scholar] [CrossRef] [PubMed]
[42] Chen, W., Zheng, R., Baade, P.D., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. [Google Scholar] [CrossRef] [PubMed]
[43] Kalemkerian, G.P., Loo, B.W., Akerley, W., et al. (2018) NCCN Guide-lines Insights: Small Cell Lung Cancer, Version 2.2018. Journal of the National Comprehensive Cancer Network, 16, 1171-1182. [Google Scholar] [CrossRef] [PubMed]
[44] 黄燕华, 施宇佳, 殷小伟. 小细胞肺癌组织中PLEKHA5的表达及临床意义[J]. 临床肿瘤学杂志, 2019, 24(7): 594-598.
[45] Beck, J.T., Ismail, A. and Tolomeo, C. (2014) Targeting the Phosphatidylinositol 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway: An Emerging Treatment Strategy for Squamous Cell Lung Carcinoma. Cancer Treatment Reviews, 40, 980-989. [Google Scholar] [CrossRef] [PubMed]
[46] Langevin, S.M., Koestler, D.C., Christensen, B.C., et al. (2012) Pe-ripheral Blood DNA Methylation Profiles Are Indicative of Head and Neck Squamous Cell Carcinoma: An Epige-nome-Wide Association Study. Epigenetics, 7, 291-299. [Google Scholar] [CrossRef] [PubMed]
[47] Relli, V., Trerotola, M., Guerra, E. and Alberti, S. (2018) Distinct Lung Cancer Subtypes Associate to Distinct Drivers of Tumor Progression. Oncotarget, 9, 35528-35540. [Google Scholar] [CrossRef] [PubMed]
[48] Liu, J., Adhav, R., Miao, K., et al. (2020) Characterization of BRCA1-Deficient Premalignant Tissues and Cancers Identifies Plekha5 as a Tumor Metastasis Suppressor. Nature Communications, 11, Article No. 4875. [Google Scholar] [CrossRef] [PubMed]
[49] Castellana, B., Escuin, D., Pérez-Olabarria, M., et al. (2012) Genetic Up-Regulation and Overexpression of PLEKHA7 Differentiates Invasive Lobular Carcinomas from Invasive Ductal Carcinomas. Human Pathology, 43, 1902-1909. [Google Scholar] [CrossRef] [PubMed]
[50] Tille, J.C., Ho, L., Shah, J., Seyde, O., McKee, T.A. and Citi, S. (2015) The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas. PLOS ONE, 10, e0135442. [Google Scholar] [CrossRef] [PubMed]
[51] Dillon, D.A., D’Aquila, T., Reynolds, A.B., Fearon, E.R. and Rimm, D.L. (1998) The Expression of p120ctn Protein in Breast Cancer Is Independent of Alpha- and Beta-Catenin and E-Cadherin. The American Journal of Pathology, 152, 75-82.
[52] Letessier, A., Garrido-Urbani, S., Ginestier, C., et al. (2007) Correlated Break at PARK2/FRA6E and Loss of AF-6/Afadin Protein Expression Are Associated with Poor Outcome in Breast Cancer. Oncogene, 26, 298-307. [Google Scholar] [CrossRef] [PubMed]
[53] Shibata, T., Kokubu, A., Sekine, S., Kanai, Y. and Hirohashi, S. (2004) Cytoplasmic p120ctn Regulates the Invasive Phenotypes of E-Cadherin-Deficient Breast Cancer. The American Journal of Pathology, 164, 2269-2278. [Google Scholar] [CrossRef
[54] Elloul, S., Kedrin, D., Knoblauch, N.W., Beck, A.H. and Toker, A. (2014) The Adherens Junction Protein Afadin Is an AKT Substrate That Regulates Breast Cancer Cell Migra-tion. Molecular Cancer Research, 12, 464-476. [Google Scholar] [CrossRef
[55] Yanagisawa, M., Huveldt, D., Kreinest, P., et al. (2008) A p120 Catenin Isoform Switch Affects Rho Activity, Induces Tumor Cell Invasion, and Predicts Metastatic Disease. Journal of Biological Chemistry, 283, 18344-18354. [Google Scholar] [CrossRef
[56] Kourtidis, A., Ngok, S.P. and Anastasiadis, P.Z. (2013) p120 Catenin: An Essential Regulator of Cadherin Stability, Adhesion-Induced Signaling, and Cancer Progression. Progress in Molecular Biology and Translational Science, 116, 409-432. [Google Scholar] [CrossRef
[57] Kourtidis, A., Ngok, S.P., Pulimeno, P., et al. (2015) Distinct E-Cadherin-Based Complexes Regulate Cell Behaviour through miRNA Processing or Src and p120 Catenin Activity. Nature Cell Biology, 17, 1145-1157. [Google Scholar] [CrossRef] [PubMed]
[58] Pence, L.J., Kourtidis, A., Feathers, R.W., et al. (2021) PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression. International Journal of Molecular Sciences, 22, 1275. [Google Scholar] [CrossRef] [PubMed]
[59] Rea, K., Roggiani, F., De Cecco, L., et al. (2018) Simultaneous E-cadherin and PLEKHA7 Expression Negatively Affects E-Cadherin/EGFR Mediated Ovarian Cancer Cell Growth. Journal of Experimental & Clinical Cancer Research, 37, Ar-ticle No. 146. [Google Scholar] [CrossRef] [PubMed]
[60] Aushev, V.N., Gopalakrishnan, K., Teitelbaum, S.L., et al. (2019) Tumor Expression of Environmental Chemical-Responsive Genes and Breast Cancer Mortality. Endo-crine-Related Cancer, 26, 843-851. [Google Scholar] [CrossRef
[61] Siegel, R.L., Miller, K.D. and Jemal, A. (2019) Cancer Statistics, 2019. CA: A Cancer Journal for Clinicians, 69, 7-34. [Google Scholar] [CrossRef] [PubMed]
[62] Chakradhar, S. (2015) Colorectal Cancer: 5 Big Questions. Nature, 521, S16. [Google Scholar] [CrossRef
[63] Shah, J., Guerrera, D., Vasileva, E., Sluysmans, S., Bertels, E. and Citi, S. (2016) PLEKHA7: Cytoskeletal Adaptor Protein at Center Stage in Junctional Organization and Signaling. The Inter-national Journal of Biochemistry & Cell Biology, 75, 112-116. [Google Scholar] [CrossRef] [PubMed]
[64] Paschoud, S., Jond, L., Guerrera, D. and Citi, S. (2014) PLEKHA7 Modulates Epithelial Tight Junction Barrier Function. Tissue Barriers, 2, e28755. [Google Scholar] [CrossRef] [PubMed]
[65] Rusu, A.D. and Georgiou, M. (2020) The Multifarious Regulation of the Apical Junctional Complex. Open Biology, 10, Article ID: 190278. [Google Scholar] [CrossRef] [PubMed]
[66] Bischoff, S.C., Barbara, G., Buurman, W., et al. (2014) Intestinal Per-meability—A New Target for Disease Prevention and Therapy. BMC Gastroenterology, 14, Article No.189. [Google Scholar] [CrossRef] [PubMed]
[67] Citi, S. (2018) Intestinal Barriers Protect against Disease. Science, 359, 1097-1098. [Google Scholar] [CrossRef] [PubMed]
[68] Coskun, M. (2014) Intestinal Epithelium in Inflammatory Bowel Dis-ease. Frontiers in Medicine (Lausanne), 1, Article No. 24. [Google Scholar] [CrossRef] [PubMed]
[69] Landy, J., Ronde, E., English, N., et al. (2016) Tight Junctions in Inflammatory Bowel Diseases and Inflammatory Bowel Disease Associated Colorectal Cancer. World Journal of Gastroenterology, 22, 3117-3126. [Google Scholar] [CrossRef] [PubMed]
[70] Daulagala, A.C., Bridges, M.C. and Kourtidis, A. (2019) E-Cadherin beyond Structure: A Signaling Hub in Colon Homeostasis and Disease. International Journal of Molecular Sciences, 20, 2756. [Google Scholar] [CrossRef] [PubMed]
[71] Kourtidis, A., Necela, B., Lin, W.H., et al. (2017) Cadherin Complexes Recruit mRNAs and RISC to Regulate Epithelial Cell Signaling. Journal of Cell Biology, 216, 3073-3085. [Google Scholar] [CrossRef] [PubMed]
[72] Nair-Menon, J., Daulagala, A.C., Connor, D.M., et al. (2020) Pre-dominant Distribution of the RNAi Machinery at Apical Adherens Junctions in Colonic Epithelia Is Disrupted in Cancer. International Journal of Molecular Sciences, 21, 2559. [Google Scholar] [CrossRef] [PubMed]
[73] Jeung, H.C., Puentes, R., Aleshin, A., et al. (2021) PLEKHA7 Signaling Is Necessary for the Growth of Mutant KRAS Driven Colo-rectal Cancer. Experimental Cell Research, 409, Article ID: 112930. [Google Scholar] [CrossRef] [PubMed]
[74] Tomassetti, A., De Santis, G., Castellano, G., et al. (2008) Vari-ant HNF1 Modulates Epithelial Plasticity of Normal and Transformed Ovary Cells. Neoplasia, 10, 1481-1492. [Google Scholar] [CrossRef] [PubMed]
[75] De Santis, G., Miotti, S., Mazzi, M., Canevari, S. and Tomassetti, A. (2009) E-Cadherin Directly Contributes to PI3K/AKT Activation by Engaging the PI3K-p85 Regulatory Subunit to Adherens Junctions of Ovarian Carcinoma Cells. Oncogene, 28, 1206-1217. [Google Scholar] [CrossRef] [PubMed]
[76] Miow, Q.H., Tan, T.Z., Ye, J., et al. (2015) Epithelial-Mesenchymal Status Renders Differential Responses to Cisplatin in Ovarian Cancer. Oncogene, 34, 1899-1907. [Google Scholar] [CrossRef] [PubMed]
[77] Tothill, R.W., Tinker, A.V., George, J., et al. (2008) Novel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer Linked to Clinical Out-come. Clinical Cancer Research, 14, 5198-5208. [Google Scholar] [CrossRef
[78] Mateescu, B., Batista, L., Cardon, M., et al. (2011) miR-141 and miR-200a Act on Ovarian Tumorigenesis by Controlling Oxidative Stress Response. Nature Medicine, 17, 1627-1635. [Google Scholar] [CrossRef] [PubMed]