DOI: 10.3724/SP.J.1206.2011.00284

Progress in Biochemistry and Biophysics (生物化学与生物物理进展) 2012/39:4 PP.307-313

Epithelial-mesenchymal Transition During Tumor Metastasis, Embryonic Development and Female Mammalian Reproduction*

Epithelial-mesenchymal transition(EMT) is a process that epithelial cells lose polarity, become mesenchymal cells and acquire the ability of migration and invasion. It exists in many physiological and pathological processes. EMT is involved in a number of signal transduction pathways and performs different physiological functions. During the early stages of embryonic development, both EMT and MET(mesenchymal- epithelial transition) contribute to the formation and development of organs. Moreover, EMT can promote tumor metastasis. EMT also occurs in female mammalian reproduction. In the ovary, EMT is beneficial for repairing process following ovulation. During decidualization, MET may be required for successful uterine anchorage of the embryo. Placental development undergoes an EMT in order to facilitate nutrient and gas exchange between mother and fetus. The failure of EMT process may cause related reproductive diseases.

Key words:EMT, tumor metastasis, embryonic development, ovary, uterus, placenta

ReleaseDate:2014-07-21 16:17:43

Funds:This work was supported by a grant from The National Natural Science Foundation of China (30930013)

[1] Thiery J P, Sleeman J P. Complex networks orchestrate epithelial- mesenchymal transitions. Nat Rev Mol Cell Biol, 2006, 7(2):131- 142

[2] Haraguchi M, Okubo T, Miyashita Y, et al. Snail regulates cell- matrix adhesion by regulation of the expression of integrins and basement membrane proteins. J Biol Chem, 2008, 283(35):23514- 23523

[3] Kalluri R, Weinberg R A. The basics of epithelial-mesenchymal transition. J Clin Invest, 2009, 119(6):1420-1428

[4] Nieman M T, Prudoff R S, Johnson K R, et al. N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol, 1999, 147(3):631-644

[5] Moustakas A, Heldin C H. Signaling networks guiding epithelial- mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci, 2007, 98(10): 1512-1520

[6] Colomiere M, Ward A C, Riley C, et al. Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial- mesenchymal transition in ovarian carcinomas. Br J Cancer, 2009, 100(1): 134-144

[7] Yook J I, Li X Y, Ota I, et al. Wnt-dependent regulation of the E-cadherin repressor snail. J Biol Chem, 2005, 280(12): 11740- 11748

[8] Zavadil J, Bottinger E P. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene, 2005, 24(37): 5764-5774

[9] Huber M A, Azoitei N, Baumann B, et al. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest, 2004, 114(4): 569-581

[10] Huber M A, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol, 2005, 17(5): 548-558

[11] Karhadkar S S, Bova G S, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature, 2004, 431(7009): 707-712

[12] Gregory P A, Bert A G, Paterson E L, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol, 2008, 10(5): 593-601

[13] Korpal M, Lee E S, Hu G, et al. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem, 2008, 283(22): 14910-14914

[14] Gebeshuber C A, Zatloukal K, Martinez J. miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep, 2009, 10(4): 400-405

[15] Du J, Yang S, An D, et al. BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1. Cell Res, 2009, 19(4): 487-496

[16] Li Q, Kannan A, Wang W, et al. Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. J Biol Chem, 2007, 282(43): 31725-31732

[17] Khew-Goodall Y, Goodall G J. Myc-modulated miR-9 makes more metastases. Nat Cell Biol, 2010, 12(3): 209-211

[18] Miles F L, Pruitt F L, van Golen K L, et al. Stepping out of the flow: capillary extravasation in cancer metastasis. Clin Exp Metastasis, 2008, 25(4): 305-324

[19] Orlichenko L S, Radisky D C. Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development. Clin Exp Metastasis, 2008, 25(6): 593-600

[20] Chaffer C L, Weinberg R A. A perspective on cancer cell metastasis. Science, 2011, 331(6024): 1559-1564

[21] Savagner P. The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol, 2010, 21(Suppl 7): vii89-vii92

[22] Nakaya Y, Sheng G. Epithelial to mesenchymal transition during gastrulation: an embryological view. Dev Growth Differ, 2008, 50(9): 755-766

[23] Duband J L, Monier F, Delannet M, et al. Epithelium-mesenchyme transition during neural crest development. Acta Anat (Basel), 1995, 154(1): 63-78

[24] Ahmed N, Thompson E W, Quinn M A. Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: an exception to the norm. J Cell Physiol, 2007, 213(3):581-588

[25] Ponnusamy M P, Lakshmanan I, Jain M, et al. MUC4 mucin- induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cells. Oncogene, 2010, 29(42): 5741-5754

[26] Park S H, Cheung L W, Wong A S, et al. Estrogen regulates Snail and Slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor alpha. Mol Endocrinol, 2008, 22(9): 2085-2098

[27] Vergara D, Merlot B, Lucot J P, et al. Epithelial-mesenchymal transition in ovarian cancer. Cancer Lett, 2010, 291(1): 59-66

[28] Paria B C, Zhao X, Das S K, et al. Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus with the initiation of implantation and decidualization. Dev Biol, 1999, 208(2): 488-501

[29] Fu J, Lv X, Lin H, et al. Ubiquitin ligase cullin 7 induces epithelial- mesenchymal transition in human choriocarcinoma cells. J Biol Chem, 2010, 285(14): 10870-10879

[30] Abell A N, Granger D A, Johnson N L, et al. Trophoblast stem cell maintenance by fibroblast growth factor 4 requires MEKK4 activation of Jun N-terminal kinase. Mol Cell Biol, 2009, 29(10):2748-2761