Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells

被引:63
作者
Wang, Yuli [1 ,2 ]
Liu, Yueyong [3 ]
Lu, Jing [1 ,2 ]
Zhang, Pengju [3 ,4 ]
Wang, Yunshan [1 ,2 ]
Xu, Yangyang [1 ,2 ]
Wang, Zeran [3 ]
Mao, Jian-Hua [3 ]
Wei, Guangwei [1 ,2 ,3 ]
机构
[1] Shandong Univ, Sch Med, Dept Anat, Minist Educ, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Sch Med, Minist Educ, Key Lab Expt Teratol, Jinan 250012, Shandong, Peoples R China
[3] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
[4] Shandong Univ, Sch Med, Dept Biochem & Mol Biol, Jinan 250012, Shandong, Peoples R China
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
Fbxw7; Epithelial-mesenchymal transition; Cell migration and invasion; Cancer stem cell; Colorectal cancer; TUMOR-SUPPRESSOR; UBIQUITIN LIGASE; AURORA-A; FBW7; DEGRADATION; METASTASIS; MTOR; PTEN; MICE;
D O I
10.1016/j.bbrc.2013.03.077
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Increased cell migration and invasion lead to cancer metastasis and are crucial to cancer prognosis. In this study, we explore whether FBXW7 plays any role in metastatic process. We show that depletion of FBXW7 induces epithelial-mesenchymal transition (EMT) in human colon cancer cells along with the increase in cell migration and invasion. Moreover, FBXW7 deficiency promotes the generation of colon cancer stem-like cells in tumor-sphere culture. mTOR inhibition by rapamycin suppresses FBXW7 loss-driven EMT, invasion and stemness. Our results define the FBXW7/mTOR axis as a novel EMT pathway that mediates cancer invasion. Published by Elsevier Inc.
引用
收藏
页码:352 / 356
页数:5
相关论文
共 23 条
[1]   Mechanisms of chemoresistance in cancer stem cells [J].
Abdullah, Lissa Nurrul ;
Chow, Edward Kai-Hua .
CLINICAL AND TRANSLATIONAL MEDICINE, 2013, 2
[2]   Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway [J].
Arabi, Azadeh ;
Ullah, Karim ;
Branca, Rui M. M. ;
Johansson, Johan ;
Bandarra, Daniel ;
Haneklaus, Moritz ;
Fu, Jing ;
Aries, Ingrid ;
Nilsson, Peter ;
Den Boer, Monique L. ;
Pokrovskaja, Katja ;
Grander, Dan ;
Xiao, Gutian ;
Rocha, Sonia ;
Lehtio, Janne ;
Sangfelt, Olle .
NATURE COMMUNICATIONS, 2012, 3
[3]   Role of the ubiquitin ligase Fbw7 in cancer progression [J].
Cheng, Yabin ;
Li, Gang .
CANCER AND METASTASIS REVIEWS, 2012, 31 (1-2) :75-87
[4]  
D'Assoro A.B., 2013, ONCOGENE
[5]   mTORC1 and mTORC2 Regulate EMT, Motility, and Metastasis of Colorectal Cancer via RhoA and Rac1 Signaling Pathways [J].
Gulhati, Pat ;
Bowen, Kanika A. ;
Liu, Jianyu ;
Stevens, Payton D. ;
Rychahou, Piotr G. ;
Chen, Min ;
Lee, Eun Y. ;
Weiss, Heidi L. ;
O'Connor, Kathleen L. ;
Gao, Tianyan ;
Evers, B. Mark .
CANCER RESEARCH, 2011, 71 (09) :3246-3256
[6]   Pten Regulates Aurora-A and Cooperates with Fbxw7 in Modulating Radiation-Induced Tumor Development [J].
Kwon, Yong-Won ;
Kim, Il-Jin ;
Wu, Di ;
Lu, Jing ;
Stock, William A. ;
Liu, Yueyong ;
Huang, Yurong ;
Kang, Hio Chung ;
DelRosario, Reyno ;
Jen, Kuang-Yu ;
Perez-Losada, Jesus ;
Wei, Guangwei ;
Balmain, Allan ;
Mao, Jian-Hua .
MOLECULAR CANCER RESEARCH, 2012, 10 (06) :834-844
[7]  
Lee YY, 2012, CANCER RES, V72, DOI [10.1158/1538-7445.AM2012-4651, 10.1158/0008-5472.CAN-12-2397]
[8]   Temporal mTOR inhibition protects Fbxw7-deficient mice from radiation-induced tumor development [J].
Liu, Yueyong ;
Huang, Yurong ;
Wang, Zeran ;
Huang, Yong ;
Li, Xiaohua ;
Louie, Alexander ;
Wei, Guangwei ;
Mao, Jian-Hua .
AGING-US, 2013, 5 (02) :111-119
[9]   MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs [J].
Lu, Dong ;
Davis, Matthew P. A. ;
Abreu-Goodger, Cei ;
Wang, Wei ;
Campos, Lia S. ;
Siede, Julia ;
Vigorito, Elena ;
Skarnes, William C. ;
Dunham, Ian ;
Enright, Anton J. ;
Liu, Pentao .
PLOS ONE, 2012, 7 (08)
[10]   The epithelial-mesenchymal transition generates cells with properties of stem cells [J].
Mani, Sendurai A. ;
Guo, Wenjun ;
Liao, Mai-Jing ;
Eaton, Elinor Ng. ;
Ayyanan, Ayyakkannu ;
Zhou, Alicia Y. ;
Brooks, Mary ;
Reinhard, Ferenc ;
Zhang, Cheng Cheng ;
Shipitsin, Michail ;
Campbell, Lauren L. ;
Polyak, Kornelia ;
Brisken, Cathrin ;
Yang, Jing ;
Weinberg, Robert A. .
CELL, 2008, 133 (04) :704-715