PKM2 promotes stemness of breast cancer cell by through Wnt/β-catenin pathway

被引:39
作者
Zhao, Zheng [1 ,2 ]
Song, Zhangjun [3 ]
Liao, Zijun [2 ]
Liu, Zhigang [2 ]
Sun, Haifeng [2 ]
Lei, Baoxia [2 ]
Chen, Wenjuan [2 ]
Dang, Chengxue [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Dept Oncol, Xian 710061, Shaanxi, Peoples R China
[2] Shaanxi Prov Tumor Hosp, Dept Med Oncol 3, Xian 710061, Peoples R China
[3] Shaanxi Prov Tumor Hosp, Breast Canc Program, Xian 710061, Peoples R China
关键词
Pyruvate kinase isozymes M2; Cancer stem cell; beta-Catenin; Stemness; Holoclone; SELF-RENEWAL; PROGENITOR CELLS; IDENTIFICATION; PYRUVATE; DIFFERENTIATION; EXPRESSION; LEUKEMIA; TUMORS;
D O I
10.1007/s13277-015-4121-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Metastasis is one of the main causes of breast cancer (BCa)-related deaths in female. It has been reported that cancer stem cell played an important role in metastasis. Here we first revealed a specific role of pyruvate kinase isozymes M2 (PKM2) in the stemness of breast cancer cells. Breast cancer tissue analysis confirmed the upregulation of PKM2 in breast cancer, and high PKM2 levels were associated with poor prognosis of breast cancer patients. Holoclone assay and colony formation assay significantly elucidated the role of PKM2 in the self-renewal of breast cancer cells. Moreover, PKM2 elevated the proportion of stem cell and the ability of sphere formation in breast cancer cells. PKM2 played its functional role in stemness by regulating beta-catenin. Collectively, we identified critical roles of PKM2 in the stemness of breast cancer cells which may elevate the therapeutic effect on breast cancer patients.
引用
收藏
页码:4223 / 4234
页数:12
相关论文
共 36 条
[1]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[2]   Self-renewal and solid tumor stem cells [J].
Al-Hajj, M ;
Clarke, MF .
ONCOGENE, 2004, 23 (43) :7274-7282
[3]   Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network [J].
Ang, Yen-Sin ;
Tsai, Su-Yi ;
Lee, Dung-Fang ;
Monk, Jonathan ;
Su, Jie ;
Ratnakumar, Kajan ;
Ding, Junjun ;
Ge, Yongchao ;
Darr, Henia ;
Chang, Betty ;
Wang, Jianlong ;
Rendl, Michael ;
Bernstein, Emily ;
Schaniel, Christoph ;
Lemischka, Ihor R. .
CELL, 2011, 145 (02) :183-197
[4]  
[Anonymous], SCI STKE
[5]   Telomerase and cancer stem cells [J].
Armanios, M. ;
Greider, C. W. .
Molecular Approaches to Controlling Cancer, 2005, 70 :205-208
[6]   3 CLONAL TYPES OF KERATINOCYTE WITH DIFFERENT CAPACITIES FOR MULTIPLICATION [J].
BARRANDON, Y ;
GREEN, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (08) :2302-2306
[7]   Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].
Bonnet, D ;
Dick, JE .
NATURE MEDICINE, 1997, 3 (07) :730-737
[8]  
BRINCK U, 1994, VIRCHOWS ARCH, V424, P177
[9]   Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features [J].
Creighton, Chad J. ;
Li, Xiaoxian ;
Landis, Melissa ;
Dixon, J. Michael ;
Neumeister, Veronique M. ;
Sjolund, Ashley ;
Rimm, David L. ;
Wong, Helen ;
Rodriguez, Angel ;
Herschkowitz, Jason I. ;
Fan, Cheng ;
Zhang, Xiaomei ;
He, Xiaping ;
Pavlick, Anne ;
Gutierrez, M. Carolina ;
Renshaw, Lorna ;
Larionov, Alexey A. ;
Faratian, Dana ;
Hilsenbeck, Susan G. ;
Perou, Charles M. ;
Lewis, Michael T. ;
Rosen, Jeffrey M. ;
Chang, Jenny C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (33) :13820-13825
[10]   Tumour stem cells and drug resistance [J].
Dean, M ;
Fojo, T ;
Bates, S .
NATURE REVIEWS CANCER, 2005, 5 (04) :275-284