title: Reactivation of Syk gene by AZA suppresses metastasis but not proliferation of breast cancer cells.
abstract: Spleen tyrosine kinase (Syk) is reported to be involved in the suppression of proliferation and invasion of breast cancer. Methylation-mediated Syk gene silencing is found in a subset of breast cancer. In this study, we used a DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine (AZA), to restore Syk expression of breast cancer cells. Surprisingly, we found that AZA treatment could reestablish the expression of Syk, but not affect the proliferation of breast cancer cells. Moreover, tumor formation in situ by MDA-MB-435s treated with (+) or without (-) AZA in a nude mice MFP (Mammary fat pad) model did not show significant difference, too. Interestingly, pulmonary metastasis was still significantly suppressed in MDA-MB-435s(+) group (1/9 vs. 7/9). Our findings suggested Syk may be more correlated to metastasis rather than proliferation. This study implied a potential use of Syk methylation as a valuable biomarker to detect high metastatic potential cancerous lesions and the prospect of AZA to join the arsenal of drug candidates to be developed as a new reagent for management of advanced breast cancer.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, People's Republic of China.
authors.forename: Tian-Song
authors.initials: TS
authors.lastname: Xia
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Shi
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Xiao-An
authors.initials: XA
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yue-Xian
authors.initials: YX
authors.lastname: Liu
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Xia
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Ding
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D000077209:Decitabine; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D000072377:Syk Kinase
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D000077209:Decitabine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D001374:Azacitidine