Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits (original) (raw)
Baum, B., Settleman, J. & Quinlan, M. P. Transitions between epithelial and mesenchymal states in development and disease. Semin. Cell Dev. Biol.19, 294–308 (2008). CASPubMed Google Scholar
Hugo, H. et al. Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J. Cell Physiol.213, 374–383 (2007). CASPubMed Google Scholar
Thiery, J. P. & Sleeman, J. P. Complex networks orchestrate epithelial–mesenchymal transitions. Nature Rev. Mol. Cell Biol.7, 131–142 (2006). CAS Google Scholar
Yang, J. & Weinberg, R. A. Epithelial–mesenchymal transition: at the crossroads of development and tumor metastasis. Dev. Cell14, 818–829 (2008). CASPubMed Google Scholar
Mani, S. A. et al. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell133, 704–715 (2008). This manuscript is the first demonstration that EMT leads to the generation of breast cancer cells with stem cell-like characteristics. CASPubMedPubMed Central Google Scholar
Morel, A. P. et al. Generation of breast cancer stem cells through epithelial–mesenchymal transition. PLoS ONE3, e2888 (2008). PubMedPubMed Central Google Scholar
Sabbah, M. et al. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist. Updat.11, 123–151 (2008). CASPubMed Google Scholar
Peinado, H., Olmeda, D. & Cano, A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature Rev. Cancer7, 415–428 (2007). CAS Google Scholar
Dumont, N. et al. Sustained induction of epithelial to mesenchymal transition activates DNA methylation of genes silenced in basal-like breast cancers. Proc. Natl Acad. Sci. USA105, 14867–14872 (2008). CASPubMedPubMed Central Google Scholar
James, D., Levine, A. J., Besser, D. & Hemmati-Brivanlou, A. TGFβ/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development132, 1273–1282 (2005). ArticleCASPubMed Google Scholar
Ozdamar, B. et al. Regulation of the polarity protein Par6 by TGFβ receptors controls epithelial cell plasticity. Science307, 1603–1609 (2005). CASPubMed Google Scholar
Vincan, E. & Barker, N. The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clin. Exp. Metastasis25, 657–663 (2008). CASPubMed Google Scholar
Vogelstein, B. & Kinzler, K. W. Cancer genes and the pathways they control. Nature Med.10, 789–799 (2004). CASPubMed Google Scholar
Lombaerts, M. et al. E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. Br. J. Cancer94, 661–671 (2006). CASPubMedPubMed Central Google Scholar
Onder, T. T. et al. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res.68, 3645–3654 (2008). CASPubMed Google Scholar
Zhang, W. et al. Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer. Cancer Res.68, 2764–2772 (2008). CASPubMedPubMed Central Google Scholar
Suzuki, H. et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nature Genet.36, 417–422 (2004). CASPubMed Google Scholar
Caldwell, G. M. et al. The Wnt antagonist sFRP1 in colorectal tumorigenesis. Cancer Res.64, 883–888 (2004). CASPubMed Google Scholar
Aguilera, O. et al. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. Oncogene25, 4116–4121 (2006). CASPubMed Google Scholar
Bailey, J. M., Singh, P. K. & Hollingsworth, M. A. Cancer metastasis facilitated by developmental pathways: Sonic hedgehog, Notch, and bone morphogenic proteins. J. Cell Biochem.102, 829–839 (2007). CASPubMed Google Scholar
Wang, Z. et al. Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res.66, 2778–2784 (2006). CASPubMed Google Scholar
Gort, E. H., Groot, A. J., van der Wall, E., van Diest, P. J. & Vooijs, M. A. Hypoxic regulation of metastasis via hypoxia-inducible factors. Curr. Mol. Med.8, 60–67 (2008). CASPubMed Google Scholar
Cannito, S. et al. Redox mechanisms switch on hypoxia-dependent epithelial–mesenchymal transition in cancer cells. Carcinogenesis29, 2267–2278 (2008). CASPubMed Google Scholar
Sahlgren, C., Gustafsson, M. V., Jin, S., Poellinger, L. & Lendahl, U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc. Natl Acad. Sci. USA105, 6392–6397 (2008). CASPubMedPubMed Central Google Scholar
Radisky, D. C. et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature436, 123–127 (2005). This study is the first to establish a link between EMT and reactive oxygen species generation and subsequent genomic instability. CASPubMedPubMed Central Google Scholar
Brabletz, T. et al. Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc. Natl Acad. Sci. USA98, 10356–10361 (2001). CASPubMedPubMed Central Google Scholar
Franci, C. et al. Expression of Snail protein in tumor–stroma interface. Oncogene25, 5134–5144 (2006). This is the first report describing EMT in physiologicalin vivoconditions in tumours. CASPubMed Google Scholar
Sheehan, K. M. et al. Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial–mesenchymal transition. Oncogene27, 323–331 (2008). CASPubMed Google Scholar
Yates, C. C., Shepard, C. R., Stolz, D. B. & Wells, A. Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. Br. J. Cancer96, 1246–1252 (2007). CASPubMedPubMed Central Google Scholar
Frisch, S. M. The epithelial cell default-phenotype hypothesis and its implications for cancer. Bioessays19, 705–709 (1997). CASPubMed Google Scholar
Chaffer, C. L., Thompson, E. W. & Williams, E. D. Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs185, 7–19 (2007). PubMed Google Scholar
Bloushtain-Qimron, N. et al. Cell type-specific DNA methylation patterns in the human breast. Proc. Natl Acad. Sci. USA105, 14076–14081 (2008). The first comprehensive characterization of cell type-specific DNA methylation patterns of normal breast progenitor cells and identification of epigenetically regulated transcription factors, including FOXC1, as regulators of stem cell properties. CASPubMedPubMed Central Google Scholar
Shipitsin, M. et al. Molecular definition of breast tumor heterogeneity. Cancer Cell11, 259–273 (2007). This study is the first comprehensive molecular characterization of CD44+CD24−breast cancer cells and identification of the TGFβ signalling pathway as a candidate regulator of their stem cell-like phenotype. CASPubMed Google Scholar
Dunbier, A. & Guilford, P. Hereditary diffuse gastric cancer. Adv. Cancer Res.83, 55–65 (2001). CASPubMed Google Scholar
Schrader, K. A. et al. Hereditary diffuse gastric cancer: association with lobular breast cancer. Fam. Cancer7, 73–82 (2008). PubMed Google Scholar
Berx, G. et al. E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene13, 1919–1925 (1996). CASPubMed Google Scholar
Ateeq, B., Unterberger, A., Szyf, M. & Rabbani, S. A. Pharmacological inhibition of DNA methylation induces proinvasive and prometastatic genes in vitro and in vivo. Neoplasia10, 266–278 (2008). CASPubMedPubMed Central Google Scholar
Guo, Y. et al. Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion. J. Biol. Chem.277, 41571–41579 (2002). CASPubMed Google Scholar
Moreno-Bueno, G., Portillo, F. & Cano, A. Transcriptional regulation of cell polarity in EMT and cancer. Oncogene27, 6958–6969 (2008). CASPubMed Google Scholar
Ansieau, S. et al. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell14, 79–89 (2008). An important study demonstrating a dual role for EMT-inducing transcription factors in tumorigenesis and senescence. CASPubMed Google Scholar
Perez-Losada, J. et al. Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway. Blood100, 1274–1286 (2002). CASPubMed Google Scholar
Sanchez-Martin, M. et al. SLUG (SNAI2) deletions in patients with Waardenburg disease. Hum. Mol. Genet.11, 3231–3236 (2002). CASPubMed Google Scholar
Gregory, P. A. et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biol.10, 593–601 (2008). CASPubMed Google Scholar
Gregory, P. A., Bracken, C. P., Bert, A. G. & Goodall, G. J. MicroRNAs as regulators of epithelial–mesenchymal transition. Cell Cycle7, 3112–3118 (2008). CASPubMed Google Scholar
Park, S. M., Gaur, A. B., Lengyel, E. & Peter, M. E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev.22, 894–907 (2008). An important study describing the regulation of EMT-inducing transcription factors by miRNAs. CASPubMedPubMed Central Google Scholar
Beltran, M. et al. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial–mesenchymal transition. Genes Dev.22, 756–769 (2008). An interesting study identifying a novel mechanism for the regulation of EMT through the expression of a natural antisense RNA suppressing ZEB2 expression. CASPubMedPubMed Central Google Scholar
Cano, A. & Nieto, M. A. Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends Cell Biol.18, 357–359 (2008). CASPubMed Google Scholar
Ma, L., Teruya-Feldstein, J. & Weinberg, R. A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature449, 682–688 (2007). The first study demonstrating a role for miRNAs in breast cancer metastasis. CASPubMed Google Scholar
Tavazoie, S. F. et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature451, 147–152 (2008). CASPubMedPubMed Central Google Scholar
Liu, R. et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N. Engl. J. Med.356, 217–226 (2007). CASPubMed Google Scholar
Sheridan, C. et al. CD44+, CD24− breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res.8, R59 (2006). PubMedPubMed Central Google Scholar
Graff, J. R., Gabrielson, E., Fujii, H., Baylin, S. B. & Herman, J. G. Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J. Biol. Chem.275, 2727–2732 (2000). CASPubMed Google Scholar
Nass, S. J. et al. Aberrant methylation of the estrogen receptor and E-cadherin 5′ CpG islands increases with malignant progression in human breast cancer. Cancer Res.60, 4346–4348 (2000). CASPubMed Google Scholar
Riethdorf, S. & Pantel, K. Disseminated tumor cells in bone marrow and circulating tumor cells in blood of breast cancer patients: current state of detection and characterization. Pathobiology75, 140–148 (2008). PubMed Google Scholar
Riethdorf, S., Wikman, H. & Pantel, K. Biological relevance of disseminated tumor cells in cancer patients. Int. J. Cancer123, 1991–2006 (2008). CASPubMed Google Scholar
Slade, M. J. et al. Comparison of bone marrow, disseminated tumour cells and blood-circulating tumour cells in breast cancer patients after primary treatment. Br. J. Cancer100, 160–166 (2008). PubMedPubMed Central Google Scholar
Sarrio, D. et al. Epithelial–mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res.68, 989–997 (2008). CASPubMed Google Scholar
Mani, S. A. et al. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc. Natl Acad. Sci. USA104, 10069–10074 (2007). CASPubMedPubMed Central Google Scholar
Perou, C. M. et al. Molecular portraits of human breast tumours. Nature406, 747–752 (2000). CASPubMed Google Scholar
Sorlie, T. et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA98, 10869–10874 (2001). CASPubMedPubMed Central Google Scholar
Honeth, G. et al. The CD44+/CD24− phenotype is enriched in basal-like breast tumors. Breast Cancer Res.10, R53 (2008). PubMedPubMed Central Google Scholar
Yu, F. et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell131, 1109–1123 (2007). CASPubMed Google Scholar
Li, X. et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J. Natl Cancer Inst.100, 672–679 (2008). CASPubMed Google Scholar
Barr, S. et al. Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clin. Exp. Metastasis25, 685–693 (2008). PubMedPubMed Central Google Scholar
Robson, E. J., Khaled, W. T., Abell, K. & Watson, C. J. Epithelial-to-mesenchymal transition confers resistance to apoptosis in three murine mammary epithelial cell lines. Differentiation74, 254–264 (2006). CASPubMed Google Scholar
Muerkoster, S. S. et al. Role of myofibroblasts in innate chemoresistance of pancreatic carcinoma — epigenetic downregulation of caspases. Int. J. Cancer123, 1751–1760 (2008). PubMed Google Scholar
Bertout, J. A., Patel, S. A. & Simon, M. C. The impact of O2 availability on human cancer. Nature Rev. Cancer8, 967–975 (2008). CAS Google Scholar
Husemann, Y. et al. Systemic spread is an early step in breast cancer. Cancer Cell13, 58–68 (2008). PubMed Google Scholar
Norton, L. & Massague, J. Is cancer a disease of self-seeding? Nature Med.12, 875–878 (2006). CASPubMed Google Scholar
Jones, P. A. & Takai, D. The role of DNA methylation in mammalian epigenetics. Science293, 1068–1070 (2001). CASPubMed Google Scholar
Feinberg, A. P. & Tycko, B. The history of cancer epigenetics. Nature Rev. Cancer4, 143–153 (2004). CAS Google Scholar
Herman, J. G. & Baylin, S. B. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med.349, 2042–2054 (2003). CASPubMed Google Scholar
Futscher, B. W. et al. Role for DNA methylation in the control of cell type specific maspin expression. Nature Genet.31, 175–179 (2002). CASPubMed Google Scholar
Feinberg, A. P., Ohlsson, R. & Henikoff, S. The epigenetic progenitor origin of human cancer. Nature Rev. Genet.7, 21–33 (2006). CASPubMed Google Scholar
Baylin, S. B. & Ohm, J. E. Epigenetic gene silencing in cancer-mechanims for early oncogenic pathway addiction? Nature Rev. Cancer6, 107–116 (2006). CAS Google Scholar
Holm, T. M. et al. Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell8, 275–285 (2005). CASPubMed Google Scholar
Kouzarides, T. Chromatin modifications and their function. Cell128, 693–705 (2007). CASPubMed Google Scholar
Stefani, G. & Slack, F. J. Small non-coding RNAs in animal development. Nature Rev. Mol. Cell Biol.9, 219–230 (2008). CAS Google Scholar
Filipowicz, W., Bhattacharyya, S. N. & Sonenberg, N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Rev. Genet.9, 102–114 (2008). CASPubMed Google Scholar
Garzon, R., Fabbri, M., Cimmino, A., Calin, G. A. & Croce, C. M. MicroRNA expression and function in cancer. Trends Mol. Med.12, 580–587 (2006). CASPubMed Google Scholar
Come, C. et al. Snail and slug play distinct roles during breast carcinoma progression. Clin. Cancer Res.12, 5395–5402 (2006). CASPubMed Google Scholar
Aigner, K. et al. The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression. FEBS Lett.581, 1617–1624 (2007). CASPubMedPubMed Central Google Scholar
Zhou, B. P. et al. Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial–mesenchymal transition. Nature Cell Biol.6, 931–940 (2004). CASPubMed Google Scholar
Martin, T. A., Goyal, A., Watkins, G. & Jiang, W. G. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann. Surg. Oncol.12, 488–496 (2005). PubMed Google Scholar
Elloul, S. et al. Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer103, 1631–1643 (2005). CASPubMed Google Scholar