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Src activation decouples cell division orientation from cell geometry in mammalian cells
Sun, Xiaoyan1,2,3,4; Qi, Hongsheng5; Zhang, Xiuzhen1,2,3; Li, Li1,2,3,6; Zhang, Jiaping1,2,3; Zeng, Qunli1,2,3; Laszlo, George S.7; Wei, Bo8; Li, Tianhong9; Jiang, Jianxin10; Mogilner, Alex11; Fu, Xiaobing4; Zhao, Min1,2,3
2018-07-01
Source PublicationBIOMATERIALS
ISSN0142-9612
Volume170Pages:82-94
AbstractOrientation of cell division plane plays a crucial role in morphogenesis and regeneration. Misoriented cell division underlies many important diseases, such as cancer. Studies with Drosophila and C. elegance models show that Src, a proto-oncogene tyrosine-protein kinase, is a critical regulator of this aspect of mitosis. However, the role for Src in controlling cell division orientation in mammalian cells is not well understood. Using genetic and pharmacological approaches and two extracellular signals to orient cell division, we demonstrated a critical role for Src. Either knockout or pharmacological inhibition of Src would retain the fidelity of cell division orientation with the long-axis orientation of mother cells. Conversely, re-expression of Src would decouple cell division orientation from the pre-division orientation of the long axis of mother cells. Cell division orientation in human breast and gastric cancer tissues showed that the Src activation level correlated with the degree of mitotic spindle misorientation relative to the apical surface. Examination of proteins associated with cortical actin revealed that Src activation regulated the accumulation and local density of adhesion proteins on the sites of cell-matrix attachment. By analyzing division patterns in the cells with or without Src activation and through use of a mathematical model, we further support our findings and provide evidence for a previously unknown role for Src in regulating cell division orientation in relation to the pre-division geometry of mother cells, which may contribute to the misoriented cell division. (C) 2018 Elsevier Ltd. All rights reserved.
KeywordCell division orientation Src Cell geometry Mitosis Cell polarity
DOI10.1016/j.biomaterials.2018.03.052
Language英语
Funding ProjectNIH[1R01EY019101] ; AFOSR[FA9550-16-1-0052] ; Research to Prevent Blindness ; NSFC[30901564] ; NSFC[81101883] ; NSFC[81721092] ; NSFC[81372067] ; NSFC[81230041] ; NSFC[81121004] ; NSFC[81421064] ; National Basic Science and Development Programme (973 Programme)[2012CB518105] ; Beijing Novel Program[2008B53] ; Beijing Novel Program[2009A38] ; National Key R&D Program of China[2017YFC1103304] ; National Key R&D Program of China[2016YFA0101000] ; National Key R&D Program of China[2016YFA0101002]
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, Biomaterials
WOS IDWOS:000432903300008
PublisherELSEVIER SCI LTD
Citation statistics
Document Type期刊论文
Identifierhttp://ir.amss.ac.cn/handle/2S8OKBNM/30451
Collection系统科学研究所
Affiliation1.Univ Calif Davis, Inst Regenerat Cures, Davis, CA 95616 USA
2.Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA
3.Univ Calif Davis, Dept Ophthalmol, Davis, CA 95616 USA
4.Chinese Peoples Liberat Army Gen Hosp, Postgrad Med Sch, Inst Basic Med Sci, Trauma Ctr,Wound Healing & Cell Biol Lab, 28 Fu Xing Rd, Beijing 100853, Peoples R China
5.Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, 55 Zhongguancun East Rd, Beijing 100190, Peoples R China
6.Third Mil Med Univ, Doping Hosp, Dept Resp Dis, Chongqing 400042, Peoples R China
7.Fred Hutchinson Canc Res Ctr, Clin Res Div, 1100 Fairview Ave, Seattle, WA USA
8.Chinese Peoples Liberat Army Gen Hosp, Dept Gen Surg, 28 Fu Xing Rd, Beijing 100853, Peoples R China
9.Univ Calif Davis, Comprehens Canc Ctr, Div Hematol Oncol, 4501 X St 3016, Sacramento, CA 95817 USA
10.Third Mil Med Univ, Inst Surg, Doping Hosp, State Key Lab Trauma Burns & Combined Injury Res, Chongqing 400042, Peoples R China
11.NYU, Dept Biol, Courant Inst, 251 Mercer St, New York, NY 10003 USA
Recommended Citation
GB/T 7714
Sun, Xiaoyan,Qi, Hongsheng,Zhang, Xiuzhen,et al. Src activation decouples cell division orientation from cell geometry in mammalian cells[J]. BIOMATERIALS,2018,170:82-94.
APA Sun, Xiaoyan.,Qi, Hongsheng.,Zhang, Xiuzhen.,Li, Li.,Zhang, Jiaping.,...&Zhao, Min.(2018).Src activation decouples cell division orientation from cell geometry in mammalian cells.BIOMATERIALS,170,82-94.
MLA Sun, Xiaoyan,et al."Src activation decouples cell division orientation from cell geometry in mammalian cells".BIOMATERIALS 170(2018):82-94.
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