The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation

doi:10.18632/oncotarget.11402

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 国家新药筛选中心

	The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation
	Zhang, Nianzhu 2; Liu, Lu 1; Fan, Ning 1; Zhang, Qian 2; Wang, Weijie 2; Zheng, Mingnan 3; Ma, Lingfei 4; Li, Yan 1; Shi, Lei 2,5
刊名	ONCOTARGET
	2016-09-20
卷号	7 期号:38 页码:61587-61600
关键词	septin forchlorfenuron breast cancer invasion MAPK
ISSN号	1949-2553
DOI	10.18632/oncotarget.11402
文献子类	Article
英文摘要	Septins are a novel class of GTP-binding cytoskeletal proteins evolutionarily conserved from yeast to mammals and have now been found to play a contributing role in a broad range of tumor types. However, their functional importance in breast cancer remains largely unclear. Here, we demonstrated that pharmaceutical inhibition of global septin dynamics would greatly suppress proliferation, migration and invasiveness in breast cancer cell lines. We then examined the expression and subcellular distribution of the selected septins SEPT2 and SEPT7 in breast cancer cells, revealing a rather variable localization of the two proteins with cell cycle progression. To determine the role of both septins in mediating malignant behavior of cancer cells, we used RNA silencing to specifically deplete endogenous SEPT2 or SEPT7 in highly invasive breast cancer cell line MDA-MB-231. Our findings showed that SEPT2/7 depletion had virtually identical inhibitory effects on cellular proliferation, apoptosis, migration and invasion. Moreover, the opposite performance in migration and invasion was observed after enforced expression of SEPT2/7 in the same cell line. We further demonstrated MEK/ERK activation, but not other MAPKs and AKT, was positively correlated with the protein levels of SEPT2 and SEPT7. Additionally, in SEPT2/7-overexpressing cells, the MEK specific inhibitor U0126 was able to correct the high active status of MEK/ERK while normalizing the increased invasive behaviors of these cells. Taken together, these results strongly suggest that SEPT2 and SEPT7 are involved in breast carcinogenesis and may serve as valuable therapeutic targets for breast cancer.
资助项目	National Natural Science Foundation of China[81402385] ; National Natural Science Foundation of China[81570236] ; doctoral Scientific Research Function of Liao Ning province[2014114] ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry[00000000] ; State Key Laboratory of Drug Research[SIMM1601KF-14]
WOS关键词	MAMMALIAN SEPTIN ; DOWN-REGULATION ; BRAIN-TUMORS ; EXPRESSION ; CELLS ; GROWTH ; ORGANIZATION ; PHOSPHORYLATION ; ANGIOGENESIS ; CILIOGENESIS
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	IMPACT JOURNALS LLC
WOS记录号	WOS:000387164700059
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275887]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ma, Lingfei; Li, Yan; Shi, Lei
作者单位	1.Dalian Med Univ, Coll Basic Med Sci, Dalian 116044, Liaoning, Peoples R China; 2.Dalian Med Univ, Inst Canc Stem Cell, Ctr Canc, Dalian 116044, Liaoning, Peoples R China; 3.Dalian Med Univ, Dalian Municipal Cent Hosp, Dept Gynecol & Obstet, Dalian 116033, Liaoning, Peoples R China; 4.Dalian Med Univ, Affiliated Hosp 1, Dalian 116011, Liaoning, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Nianzhu,Liu, Lu,Fan, Ning,et al. The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation[J]. ONCOTARGET,2016,7(38):61587-61600.
APA	Zhang, Nianzhu.,Liu, Lu.,Fan, Ning.,Zhang, Qian.,Wang, Weijie.,...&Shi, Lei.(2016).The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation.ONCOTARGET,7(38),61587-61600.
MLA	Zhang, Nianzhu,et al."The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation".ONCOTARGET 7.38(2016):61587-61600.