The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells: A Coalition Against Cancer Therapies

被引:367
作者
Hollier, Brett G. [1 ]
Evans, Kurt [1 ]
Mani, Sendurai A. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Unit 951, Houston, TX 77054 USA
关键词
Epithelial; Mesenchymal; Breast cancer; Metastasis; Stem cell; Therapy resistance; HUMAN BREAST-CANCER; TRANSCRIPTION FACTOR SNAIL; ACUTE MYELOID-LEUKEMIA; IN-VITRO PROPAGATION; GROWTH-FACTOR-BETA; GENE-EXPRESSION; E-CADHERIN; MAMMARY-GLAND; CONFERS RESISTANCE; METAPLASTIC CARCINOMAS;
D O I
10.1007/s10911-009-9110-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
During cancer progression, some cells within the primary tumor may reactivate a latent embryonic program known as epithelial-to-mesenchymal transition (EMT). Through EMT, transformed epithelial cells can acquire the mesenchymal traits that seem to facilitate metastasis. Indeed, there is accumulating evidence that EMT and mesenchymal-related gene expression are associated with aggressive breast cancer subtypes and poor clinical outcome in breast cancer patients. More recently, the EMT program was shown to endow normal and transformed mammary epithelial cells with stem cell properties, including the ability to self-renew and efficiently initiate tumors. This link between EMT and stem cells may have numerous implications in the progression of breast tumors. The EMT process may facilitate the generation of cancer cells with the mesenchymal traits needed for dissemination as well as the self-renewal properties needed for initiation of secondary tumors. Breast cancer stem cells are resistant to many conventional cancer therapies, which can promote tumor relapse. Therefore, the generation of cancer stem cells by EMT may promote the development of refractory and resistant breast tumors. The purpose of this review is to summarize the findings related to EMT and stem cells in cancer progression and therapy resistance.
引用
收藏
页码:29 / 43
页数:15
相关论文
共 142 条
[1]
Differential cadherin expression: Potential markers for epithelial to mesenchymal transformation during tumor progression [J].
Agiostratidou, Georgia ;
Hulit, James ;
Phillips, Greg R. ;
Hazan, Rachel B. .
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 2007, 12 (2-3) :127-133
[2]
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
[3]
Challenges in the development of anti-epidermal growth factor receptor therapies in breast cancer [J].
Arteaga, CL ;
Truica, CI .
SEMINARS IN ONCOLOGY, 2004, 31 (01) :3-8
[4]
Phosphatidylinositol 3-kinase function is required for transforming growth factor β-mediated epithelial to mesenchymal transition and cell migration [J].
Bakin, AV ;
Tomlinson, AK ;
Bhowmick, NA ;
Moses, HL ;
Arteaga, CL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (47) :36803-36810
[5]
Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype [J].
Balic, Marija ;
Lin, Henry ;
Young, Lillian ;
Hawes, Debra ;
Giuliano, Armando ;
McNamara, George ;
Datar, Ram H. ;
Cote, Richard J. .
CLINICAL CANCER RESEARCH, 2006, 12 (19) :5615-5621
[6]
The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells [J].
Batlle, E ;
Sancho, E ;
Franci, C ;
Domínguez, D ;
Monfar, M ;
Baulida, J ;
de Herreros, AG .
NATURE CELL BIOLOGY, 2000, 2 (02) :84-89
[7]
Transitions between epithelial and mesenchymal states in development and disease [J].
Baum, Buzz ;
Settleman, Jeffrey ;
Quinlan, Margaret P. .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2008, 19 (03) :294-308
[8]
THE PRIMITIVE STREAK [J].
BELLAIRS, R .
ANATOMY AND EMBRYOLOGY, 1986, 174 (01) :1-14
[9]
Correlation of Snail expression with histological grade and lymph node status in breast carcinomas [J].
Blanco, MJ ;
Moreno-Bueno, G ;
Sarrio, D ;
Locascio, A ;
Cano, A ;
Palacios, J ;
Nieto, MA .
ONCOGENE, 2002, 21 (20) :3241-3246
[10]
Epithelial mesenchymal transition traits in human breast cancer cell lines [J].
Blick, T. ;
Widodo, E. ;
Hugo, H. ;
Waltham, M. ;
Lenburg, M. E. ;
Neve, R. M. ;
Thompson, E. W. .
CLINICAL & EXPERIMENTAL METASTASIS, 2008, 25 (06) :629-642