Regulación de la angiogénesis por antioxidantes en el cáncer de mama triple negativo
DOI:
https://doi.org/10.19136/jobs.a10n27.6329Palabras clave:
Cáncer de mama triple negativo, Angiogénesis, Antioxidante, Tratamiento alternativoResumen
El cáncer de mama triple negativo (CMTN) está relacionado con un peor pronóstico y un comportamiento más agresivo. Este subtipo cuenta con una mayor frecuencia de metástasis, la cual se ve favorecida por el proceso vascularización relacionado a la angiogénesis tumoral. El objetivo del estudio fue realizar un análisis de expresión diferencial y ontología de genes (GO) en células MDA-MB-468 en respuesta al tratamiento con el antioxidante CAT-SKL, el análisis se realizó utilizando secuencias públicas contenidas en la base de datos Gene Expression Omnibus (GEO). La angiogénesis fue una de las ontologías que resultó subexpresada (DR) por el tratamiento con CAT-SKL. Los genes proangiogénicos KDR, EGR3, CCN2, S100A7, PDGFRA y FN1 se observaron disminuidos, mientras que el gen antiangiogénico IL18 se mantuvo incrementado. Adicionalmente encontramos que ontologías relacionadas con el transporte de aminoácidos se presentan sobreexpresadas (UR).
Referencias
Lugones, M., & Ramírez, M., “Aspectos históricos y culturales sobre el cáncer de mama”, Revista Cubana de Medicina General Integral, Vol. 25, No.3, 2009, 160–166.
Satherley, L., & Lloyd, E., “Breast cancer”, Medicine, 51, 1, 2023, 42–47. DOI: https://doi.org/10.1016/j.mpmed.2022.10.008
Siegel, R.L., Miller, L.D., Jemal, A., “Cancer statistics”, CA: A Cancer Journal for Clinicians, 66, 1, 2016, 7–30. DOI: https://doi.org/10.3322/caac.21332
Arceo, M.T., López, J.E., Ochoa, A., & Palomera, Z., “Estado actual del cáncer de mama en México: principales tipos y factores de riesgo”, Gaceta Mexicana de Oncología, 20, 3, 2021, 101–110. DOI: https://doi.org/10.24875/j.gamo.21000134
Sun, Y.S., Zhao, Z., Yang, Z.N., Xu, F., Lu, H.J., Zhu, Z.Y., et al., “Risk factors and preventions of breast cancer”, International Journal of Biological Sciences, 13, 2017, 1387–1397. DOI: https://doi.org/10.7150/ijbs.21635
Arroyo, M., Martín, M., & Álvarez-Mon, M., “Cáncer de mama”, Medicine, 12, 34, 2017, 2011–2023. DOI: https://doi.org/10.1016/j.med.2017.05.001
Tsang, J.Y.S., & Tse, G.M., “Molecular Classification of Breast Cancer”, Advances in Anatomic Pathology, 27, 1, 2020, 27–35. DOI: https://doi.org/10.1097/PAP.0000000000000232
Łukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., & Stanisławek, A., “Breast Cancer—Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies— An Updated Review”, Cancers (Basel), 13, 4287, 2021, 1–30. DOI: https://doi.org/10.3390/cancers13174287
Irvin, W.J., & Carey, L.A., “What is triple-negative breast cancer?”, European Journal of Cancer, 44, 18, 2008, 2799–2805. DOI: https://doi.org/10.1016/j.ejca.2008.09.034
Orban, M.S., Ulloa, A.L., Arias, C.P., Gon, C., Sanchotena, V., Carrasco, M., Horton, G., et al., “Cáncer de mama Triple Negativo: evaluación de características clínico-patológicas y factores pronósticos”, Revista Argentina de Mastologia, 36, 130, 2017, 73–86.
Elias, A.D., “Triple-negative breast cancer: A short review”, American Journal of Clinical Oncology: Cancer Clinical Trials, 33, 6, 2010, 637–645. DOI: https://doi.org/10.1097/COC.0b013e3181b8afcf
Zaharia, M., & Gómez, H., “Cáncer de Mama Triple Negativo: Una enfermedad de difícil diagnóstico y tratamiento”, Revista Peruana de Medicina Experimental y Salud Pública, 30, 4, 2013, 649–656. DOI: https://doi.org/10.17843/rpmesp.2013.304.247
Lopes, C.M., Montemor, M.R., Mansani, F.P, Stival, R.S.M., Cassapula, M.R., & Oliveira, T.F.B., “Clinical, histomorphological, and therapeutic prognostic factors in patients with triple-negative invasive breast cancer”, Jornal Brasileiro de Patologia e Medicina Laboratorial, 51, 6, 2015, 397–406. DOI: https://doi.org/10.5935/1676-2444.20150062
Guerra, A., Silva, E., Montero, S., Rodríguez, D., Mansilla, R., & Nieto, J., “Metástasis: un hito para el conocimiento, un reto para la ciencia”, Revista Cubana de Medicina, 59, 1, 2020, e1167.
Aslan, C., Maralbashi, S., Salari, F., Kahroba, H., Sigaroodi, F., Kazemi, T., et al., “Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy”, Journal of Cellular Physiology, 234, 10, 2019, 16885–16903. DOI: https://doi.org/10.1002/jcp.28374
Aslan, C., Maralbashi, S., Kahroba, H., Asadi, M., Soltani, M.S., Javadian, M., et al., “Docosahexaenoic acid (DHA) inhibits pro-angiogenic effects of breast cancer cells via down-regulating cellular and exosomal expression of angiogenic genes and microRNAs”, Life Sciences, 258, 2020, 118094. DOI: https://doi.org/10.1016/j.lfs.2020.118094
Shashni, B., Nishikawa, Y., & Nagasaki, Y., “Management of tumor growth and angiogenesis in triple-negative breast cancer by using redox nanoparticles”, Biomaterials, 269, 2021, 120645. DOI: https://doi.org/10.1016/j.biomaterials.2020.120645
Madu, C.O., Wang, S., Madu, C.O., & Lu, Y., “Angiogenesis in Breast Cancer Progression, Diagnosis, and Treatment”, Journal of Cancer, 11, 15, 2020, 4474–4494. DOI: https://doi.org/10.7150/jca.44313
Liang, H., Xiao, J., Zhou, Z., Wu, J., Ge, F., Li, Z., et al., “Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis”, Oncogene, 37, 15, 2018, 1961–1975. DOI: https://doi.org/10.1038/s41388-017-0089-8
Rana, N.K., Singh, P., & Koch, B., “CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis”, Biological Research, 52, 1, 2019, 12. DOI: https://doi.org/10.1186/s40659-019-0221-z
López, O., Magariño, Y., & Delgado, R., “The angiogenic process and cancer”, Biotecnología Aplicada, 26, 2, 2009, 111–116.
Vasudev, N.S., & Reynolds, A.R., “Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions”, Angiogenesis, 17, 3, 2014, 471–494. DOI: https://doi.org/10.1007/s10456-014-9420-y
Smolarz, B., Zadro, A., & Romanowicz, H., “Breast Cancer-Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature)”, Cancers (Basel), 14, 10, 2022, 1–27. DOI: https://doi.org/10.3390/cancers14102569
Olejarz, W., Kubiak, G., Chrzanowska, A., & Lorenc, T., “Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers”, International Journal of Molecular Sciences, 21, 16, 2020, 5840. DOI: https://doi.org/10.3390/ijms21165840
Ribatti, D., “Endogenous inhibitors of angiogenesis”, Leukemia Research, 33, 5, 2009, 638–644. DOI: https://doi.org/10.1016/j.leukres.2008.11.019
Wahba, H.A., & El-Hadaad, H.A., “Current approaches in treatment of triple-negative breast cancer”, Cancer Biology & Medicine, 12, 2, 2015, 106–116.
Kumar, P., & Aggarwal, R., “An overview of triple-negative breast cancer”, Archives of Gynecology and Obstetrics, 293, 2, 2016, 247–69. DOI: https://doi.org/10.1007/s00404-015-3859-y
Catalano, A., Iacopetta, D., Ceramella, J., Mariconda, A., Rosano, C., Scumaci, D., et al., “New Achievements for the Treatment of Triple-Negative Breast Cancer”, Applied Sciences, 12, 11, 2022, 5554. DOI: https://doi.org/10.3390/app12115554
Yang, Z., Zhang, Q., Yu, L., Zhu, J., Cao, Y., & Gao, X., “The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer”, Journal of Ethnopharmacology, 264, 2021, 113249. DOI: https://doi.org/10.1016/j.jep.2020.113249
Griñan, C., Blaya, J.L., López, A., Ávalos, M., Navarro, A., Cara, F.E., et al., “Antioxidants for the treatment of breast cancer: Are we there yet?”, Antioxidants, 10, 2, 2021, 1–44. DOI: https://doi.org/10.3390/antiox10020205
Szatrowski, T., & Nathan, C., “Production of large amounts of hydrogen peroxide by human tumor cells”, Cancer Research, 51, 3, 1991, 794–798.
Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., et al., “Oxidative Stress: Harms and Benefits for Human Health”, Oxidative Medicine and Cellular Longevity, 2017, 2017, 1–13. DOI: https://doi.org/10.1155/2017/8416763
Liou, G.Y., & Storz, P., “Reactive oxygen species in cancer”, Free Radical Research, 44, 5, 2010, 479–496. DOI: https://doi.org/10.3109/10715761003667554
Nell, H.J., Au, J.L., Giordano, C.R., Terlecky, S.R., Walton, P.A., Whitehead, S.N., et al., “Targeted Antioxidant, Catalase-SKL, Reduces Beta-Amyloid Toxicity in the Rat Brain”, Brain Pathology, 27, 1, 2017, 86–94. DOI: https://doi.org/10.1111/bpa.12368
Hayes, S.H., Liu, Q., Selvakumaran, S., Haney, M.J., Batrakova, E.V., Allman, B.L., et al., “Brain Targeting and Toxicological Assessment of the Extracellular Vesicle-Packaged Antioxidant Catalase-SKL Following Intranasal Administration in Mice”, Neurotoxicity Research, 39, 5, 2021, 1418–1429. DOI: https://doi.org/10.1007/s12640-021-00390-6
Giordano, C.R., Terlecky, L.J., Bollig, A., Walton, P.A., & Terlecky, S.R., “Amyloid-beta neuroprotection mediated by a targeted antioxidant”, Scientific Reports, 4, 1, 2014, 4983. DOI: https://doi.org/10.1038/srep04983
MacKenzie, J.L., Ivanova, N., Nell, H.J., Giordano, C.R., Terlecky, S.R., Agca, C., et al., “Microglial Inflammation and Cognitive Dysfunction in Comorbid Rat Models of Striatal Ischemic Stroke and Alzheimer’s Disease: Effects of Antioxidant Catalase-SKL on Behavioral and Cellular Pathology”, Neuroscience, 487, 2022, 47–65. DOI: https://doi.org/10.1016/j.neuroscience.2022.01.026
Giordano, C.R., Roberts, R., Krentz, K.A., Bissig, D., Talreja, D., Kumar, A., et al., “Catalase Therapy Corrects Oxidative Stress-Induced Pathophysiology in Incipient Diabetic Retinopathy”, Investigative Opthalmology & Visual Science, 56, 5, 2015, 3095. DOI: https://doi.org/10.1167/iovs.14-16194
Giordano, C.R., Mueller, K.L., Terlecky, L.J., Krentz, K.A., Bollig, A., Terlecky, S.R., et al., “A targeted enzyme approach to sensitization of tyrosine kinase inhibitor-resistant breast cancer cells”, Experimental Cell Research, 318, 16, 2012, 2014–2021. DOI: https://doi.org/10.1016/j.yexcr.2012.06.001
Bao, B., Mitrea, C., Wijesinghe, P., Marchetti, L., Girsch, E., Farr, R.L., et al., “Treating triple negative breast cancer cells with erlotinib plus a select antioxidant overcomes drug resistance by targeting cancer cell heterogeneity”, Scientific Reports, 7, 1, 2017, 44125. DOI: https://doi.org/10.1038/srep44125
Mitrea, C., Wijesinghe, P., Dyson, G., Kruger, A., Ruden, D.M., Drghici, S., et al., “Integrating 5hmC and gene expression data to infer regulatory mechanisms”, Bioinformatics, 34, 9, 2018, 1441–1447. DOI: https://doi.org/10.1093/bioinformatics/btx777
Andrews S., https://www.bioinformatics.babraham.ac.uk/projects/fastqc/, 2010, FASTQC, “A quality control tool for high throughput sequence data”.
Kim, D., Langmead, B., & Salzberg, S.L., “HISAT: a fast spliced aligner with low memory requirements”, Nature Methods, 12, 4, 2015, 357–360. DOI: https://doi.org/10.1038/nmeth.3317
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., et al., “The Sequence Alignment/Map format and SAMtools”, Bioinformatics, 25, 16, 2009, 2078–2079. DOI: https://doi.org/10.1093/bioinformatics/btp352
Liao, Y., Smyth, G.K., & Shi, W., “featureCounts: an efficient general purpose program for assigning sequence reads to genomic features”, Bioinformatics, 30, 7, 2014, 923–930. DOI: https://doi.org/10.1093/bioinformatics/btt656
Robinson, M.D., McCarthy, D.J., & Smyth, G.K., “edgeR: a Bioconductor package for differential expression analysis of digital gene expression data”, Bioinformatics, 26, 1, 2010, 139–140. DOI: https://doi.org/10.1093/bioinformatics/btp616
Ritchie, M.E., Phipson, B., Wu, D., Hu, Y., Law, C.W., Shi, W., et al., “limma powers differential expression analyses for RNA-sequencing and microarray studie”, Nucleic Acids Research, 43, 7, 2015, e47–e47. DOI: https://doi.org/10.1093/nar/gkv007
Raudvere, U., Kolberg, L., Kuzmin, I., Arak, T., Adler, P., Peterson, H., et al., “g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update)”, Nucleic Acids Research, 47, W1, 2019, W191–W198. DOI: https://doi.org/10.1093/nar/gkz369
The Gene Ontology C., “The Gene Ontology Resource: 20 years and still GOing strong”, Nucleic Acids Research, 47, D1, 2019, D330–D338. DOI: https://doi.org/10.1093/nar/gky1055
Androutsopoulos, V.P., Tsatsakis, A.M., Spandidos, D.A., “Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention” BMC Cancer, 9, 1, 2009, 187. DOI: https://doi.org/10.1186/1471-2407-9-187
Stading, R., Chu, C., Couroucli, X., Lingappan, K., & Moorthy, B., “Molecular role of cytochrome P4501A enzymes in oxidative stress”, Current Opinion in Toxicology, 20–21, 2020, 77–84. DOI: https://doi.org/10.1016/j.cotox.2020.07.001
Li, S., Lu, Z., Sun, R., Guo, S., Gao, F., Cao, B., et al., “The Role of SLC7A11 in Cancer: Friend or Foe?”, Cancers (Basel), 14, 13, 2022, 3059. DOI: https://doi.org/10.3390/cancers14133059
Granitzer, S., Widhalm, R., Forsthuber, M., Ellinger, I., Desoye, G., Hengstschläger, M., et al., “Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo”, International Journal of Molecular Sciences, 22, 4, 2021, 1707. DOI: https://doi.org/10.3390/ijms22041707
de la Ballina, L.R., Cano, S., González, E., Bial, S., Estrach, S., Cailleteau, L., et al., “Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability”, Journal of Biological Chemistry, 291, 18, 2016, 9700–9711. DOI: https://doi.org/10.1074/jbc.M115.704254
Fukai, T., & Ushio, M., “Cross-Talk between NADPH Oxidase and Mitochondria: Role in ROS Signaling and Angiogenesis”, Cells, 9, 8, 2020, 1849. DOI: https://doi.org/10.3390/cells9081849
Brown, N.S., & Bicknell, R., “Hypoxia and oxidative stress in breast cancer Oxidative stress - its effects on the growth, metastatic potential and response to therapy of breast cancer”, Breast Cancer Research, 3, 5, 2001, 323. DOI: https://doi.org/10.1186/bcr315
Ushio, M., & Nakamura, Y., “Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy”, Cancer Letters, 266, 1, 2008, 37–52. DOI: https://doi.org/10.1016/j.canlet.2008.02.044
Stewart, M., Turley, H., Cook, N., Pezzella, F., Pillai, G., Ogilvie, D., et al., “The angiogenic receptor KDR is widely distributed in human tissues and tumours and relocates intracellularly on phosphorylation”, An immunohistochemical study, Histopathology, 43, 1, 2003, 33–39. DOI: https://doi.org/10.1046/j.1365-2559.2003.01644.x
Liu, D., Evans, I., Britton, G., & Zachary, I., “The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis”, Oncogene, 27, 21, 2008, 2989–2998. DOI: https://doi.org/10.1038/sj.onc.1210959
Shimo, T., Nakanishi, T., Nishida, T., Asano, M., Kanyama, M., Kuboki, T., et al., “Connective Tissue Growth Factor Induces the Proliferation, Migration, and Tube Formation of Vascular Endothelial Cells In Vitro, and Angiogenesis In Vivo”, The Journal of Biochemistry, 126, 1, 1999, 137–145. DOI: https://doi.org/10.1093/oxfordjournals.jbchem.a022414
Vegfors, J., Ekman, A.K., Stoll, S.W., Bivik, C, & Enerbäck, C., “Psoriasin (S100A7) promotes stress-induced angiogenesis”, British Journal of Dermatology, 175, 6, 2016, 1263–1273. DOI: https://doi.org/10.1111/bjd.14718
Zhang, J., Cao, R., Zhang, Y., Jia, T., Cao, Y., & Wahlberg, E., “Differential roles of PDGFR‐α and PDGFR‐β in angiogenesis and vessel stability”, The FASEB Journal, 23, 1, 2009, 153–163. DOI: https://doi.org/10.1096/fj.08-113860
Xu, X., Shen, L., Li, W., Liu, X., Yang, P., & Cai, J., “ITGA5 promotes tumor angiogenesis in cervical cancer”, Cancer Medicine, 12, 10, 2023, 11983–11999. DOI: https://doi.org/10.1002/cam4.5873
Cao, R., Farnebo, J., Kurimoto, M., & Cao, Y., “Interleukin‐18 acts as an angiogenesis and tumor suppressor”, The FASEB Journal, 13, 15, 1999, 2195–2202. DOI: https://doi.org/10.1096/fasebj.13.15.2195
Modi, S.J., & Kulkarni, V.M., “Vascular Endothelial Growth Factor Receptor (VEGFR-2)/KDR Inhibitors: Medicinal Chemistry Perspective”, Medicine in Drug Discovery, 2, 2019, 100009. DOI: https://doi.org/10.1016/j.medidd.2019.100009
Zhang, X., Ge, Y.L., Zhang, S.P., Yan, P., & Tian, R.H., “Downregulation of KDR expression induces apoptosis in breast cancer cells”, Cellular & Molecular Biology Letters, 19, 4, 2014, 527–541. DOI: https://doi.org/10.2478/s11658-014-0210-8
Suzuki, T., Inoue, A., Miki, Y., Moriya, T., Akahira, J., Ishida, T., et al., “Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor”, Endocrine-Related Cancer, 14, 2, 2007, 279–292. DOI: https://doi.org/10.1677/ERC-06-0005
Shen, Y.W., Zhou, Y.D., Chen, H.Z., Luan, X., & Zhang, W.D., “Targeting CTGF in Cancer: An Emerging Therapeutic Opportunity”, Trends in Cancer, 7, 6, 2021, 511–524. DOI: https://doi.org/10.1016/j.trecan.2020.12.001
Kim, H., & Son, S., “Therapeutic potential of connective tissue growth factor (CTGF) in triple-negative breast cancer”, Annals of Oncology, 30, 2019, i8. DOI: https://doi.org/10.1093/annonc/mdz029.015
Zhou, Y., Yu, Y., Yang, H., Yang, H., Huo, Y., Huang, Y., et al., “Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF”, Cancer Science, 113, 7, 2022, 2457–2471. DOI: https://doi.org/10.1111/cas.15375
Nasser, M.W., Wani, N.A., Ahirwar, D.K., Powell, C.A., Ravi, J., Elbaz, M., et al., “RAGE Mediates S100A7-Induced Breast Cancer Growth and Metastasis by Modulating the Tumor Microenvironment”, Cancer Research, 75, 6, 2015, 974–985. DOI: https://doi.org/10.1158/0008-5472.CAN-14-2161
Joglekar, M., Van Laere, S., Bourne, M., Moalwi, M., Finetti, P., Vermeulen, P.B., et al., “Characterization and Targeting of Platelet-Derived Growth Factor Receptor alpha (PDGFRA) in Inflammatory Breast Cancer (IBC)”, Neoplasia, 19, 7, 2017, 564–573. DOI: https://doi.org/10.1016/j.neo.2017.03.002
Jansson, S., Bendahl, P.O., Grabau, D.A., Falck, A.K., Fernö, M., Aaltonen, K., et al., “The Three Receptor Tyrosine Kinases c-KIT, VEGFR2 and PDGFRα, Closely Spaced at 4q12, Show Increased Protein Expression in Triple-Negative Breast Cancer”, PLoS One, 9, 7, 2014, e102176. DOI: https://doi.org/10.1371/journal.pone.0102176
Jansson, S., Aaltonen, K., Bendahl, P.O., Falck, A.K., Karlsson, M., Pietras, K., et al., “The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence”, Breast Cancer Research and Treatment, 169, 2018, 231–241. DOI: https://doi.org/10.1007/s10549-018-4664-7
Sun, Y., Zhao, C., Ye, Y., Wang, Z., He, Y., Li, Y., et al., “High expression of fibronectin 1 indicates poor prognosis in gastric cancer”, Oncology Letters, 19, 1, 2019, 93–102. DOI: https://doi.org/10.3892/ol.2019.11088
Zhang, X.X., Luo, J.H., & Wu, L.Q., “FN1 overexpression is correlated with unfavorable prognosis and immune infiltrates in breast cancer”, Frontiers in Genetics, 13, 2022, 913659. DOI: https://doi.org/10.3389/fgene.2022.913659
Suman, S., Basak, T., Gupta, P., Mishra, S., Kumar, V., Sengupta, S., et al., “Quantitative proteomics revealed novel proteins associated with molecular subtypes of breast cancer”, Journal of Proteomics, 148, 2016, 183–193. DOI: https://doi.org/10.1016/j.jprot.2016.07.033
Yaqoob, U., Jagavelu, K., Shergill, U., de Assuncao, T., Cao, S., & Shah, V.H., “FGF21 Promotes Endothelial Cell Angiogenesis through a Dynamin-2 and Rab5 Dependent Pathway”, PLoS One, 9, 5, 2014, e98130. DOI: https://doi.org/10.1371/journal.pone.0098130
Segarra, M., Ohnuki, H., Maric, D., Salvucci, O., Hou, X., Kumar, A., et al., “Semaphorin 6A regulates angiogenesis by modulating VEGF signaling”, Blood, 120, 19, 2012, 4104–4115. DOI: https://doi.org/10.1182/blood-2012-02-410076
Cai, Y.C., Yang, H., Wang, K.F., Chen, T.H., Jiang, W.Q., & Shi, Y.X., “ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer”, BMC Cancer, 20, 2020, 878. DOI: https://doi.org/10.1186/s12885-020-07343-w
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