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      Therapeutic implications of cancer epithelial-mesenchymal transition (EMT)

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      https://www.riss.kr/link?id=A106054472

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      다국어 초록 (Multilingual Abstract)

      The epithelial-mesenchymal transition (EMT)comprises an essential biological process involving cancer progression as well as initiation. While the EMT has been regarded as a phenotypic conversion from epithelial to mesenchymal cells, recent evidence i...

      The epithelial-mesenchymal transition (EMT)comprises an essential biological process involving cancer progression as well as initiation. While the EMT has been regarded as a phenotypic conversion from epithelial to mesenchymal cells, recent evidence indicates that it plays a critical role in stemness, metabolic reprogramming, immune evasion and therapeutic resistance of cancer cells. Interestingly, several transcriptional repressors including Snail (SNAI1), Slug (SNAI2) and the ZEB family constitute key players for EMT in cancer as well as in the developmental process. Note that the dynamic conversion between EMT and epithelial reversion (mesenchymal-epithelial transition, MET) occurs through variable intermediate-hybrid states rather than being a binary process. Given the close connection between oncogenic signaling and EMT repressors, the EMT has emerged as a therapeutic target or goal (in terms of MET reversion) in cancer therapy. Here we review the critical role of EMT in therapeutic resistance and the importance of EMT as a therapeutic target for human cancer.

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      참고문헌 (Reference)

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      51 Lee SM, "Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma : SWOG 0933" 121 : 432-440, 2015

      52 Ikeda M, "Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer" 79 : 1169-1177, 2017

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      64 Arend RC, "Inhibition of Wnt/beta-catenin pathway by niclosamide : a therapeutic target for ovarian cancer" 134 : 112-120, 2014

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      68 Chockley PJ, "Immunological consequences of epithelial-mesenchymal transition in tumor progression" 197 : 691-698, 2016

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      70 Yang Q, "Idelalisib : first-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma" 21 : 1537-1542, 2015

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      72 Moreno-Bueno G, "Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for Snail, Slug, and E47 factors in epithelial-mesenchymal transition" 66 : 9543-9556, 2006

      73 Rodon J, "First-in-human dose study of the novel transforming growth factor-beta receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma" 21 : 553-560, 2015

      74 Lang L, "FDA approves sorafenib for patients with inoperable liver cancer" 134 : 379-, 2008

      75 Vogelzang NJ, "Everolimus vs. temsirolimus for advanced renal cell carcinoma : use and use of resources in the US Oncology Network" 11 : 115-120, 2013

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      79 Thiery JP, "Epithelial-mesenchymal transitions in tumour progression" 2 : 442-454, 2002

      80 Kalluri R, "Epithelial-mesenchymal transition and its implications for fibrosis" 112 : 1776-1784, 2003

      81 Arumugam T, "Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer" 69 : 5820-5828, 2009

      82 Kuczynski EA, "Effects of sorafenib dose on acquired reversible resistance and toxicity in hepatocellular carcinoma" 75 : 2510-2519, 2015

      83 Shah MA, "Effect of Fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma : the METGastric randomized clinical trial" 3 : 620-627, 2017

      84 Park CY, "EW-7203, a novel small molecule inhibitor of transforming growth factor-beta(TGFbeta)type I receptor/activin receptor-like kinase-5, blocks TGFbeta1-mediated epithelial-to-mesenchymal transition in mammary epithelial cells" 102 : 1889-1896, 2011

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      88 Haslehurst AM, "EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer" 12 : 91-, 2012

      89 Tryndyak VP, "E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells" 126 : 2575-2583, 2010

      90 Lu Z, "Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion" 4 : 499-515, 2003

      91 Kroepil F, "Downregulation of CDH1 is associated with expression of SNAI1 in colorectal adenomas" 7 : e46665-, 2012

      92 Irie HY, "Distinct roles of Akt1and Akt2 in regulating cell migration and epithelial-mesenchymal transition" 171 : 1023-1034, 2005

      93 Wilhelm S, "Discovery and development of sorafenib : a multikinase inhibitor for treating cancer" 5 : 835-844, 2006

      94 Lacouture ME, "Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor beta by the monoclonal antibody fresolimumab(GC1008)" 64 : 437-446, 2015

      95 Kim HJ, "Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail" 27 : 3165-3175, 2007

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      98 Lamouille S, "Cell size and invasion in TGF-betainduced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway" 178 : 437-451, 2007

      99 Wu ZQ, "Canonical Wnt signaling regulates Slug activity and links epithelial-mesenchymal transition with epigenetic breast cancer 1, early onset(BRCA1)repression" 109 : 16654-16659, 2012

      100 Zhu Y, "Biological and clinical significance of cancer stem cell plasticity" 3 : 32-, 2014

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      103 Hay ED, "An overview of epithelio-mesenchymal transformation" 154 : 8-20, 1995

      104 Park CY, "An novel inhibitor of TGF-beta type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition" 351 : 72-80, 2014

      105 Xie L, "Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro" 6 : 603-610, 2004

      106 Pattabiraman DR, "Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumorinitiating ability" 351 : aad3680-, 2016

      107 Yochum GS, "AXIN2: tumor suppressor, oncogene or both in colorectal cancer?" 4 : 7-8, 2012

      108 Spaderna S, "A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer" 131 : 830-840, 2006

      109 De Jesus-Acosta A, "A phase II study of the gamma secretase inhibitor RO4929097 in patients with previously treated metastatic pancreatic adenocarcinoma" 32 : 739-745, 2014

      110 Diaz-Padilla I, "A phase II study of single-agent RO4929097, a gamma-secretase inhibitor of Notch signaling, in patients with recurrent platinumresistant epithelial ovarian cancer : a study of the Princess Margaret, Chicago and California phase II consortia" 137 : 216-222, 2015

      111 Strosberg JR, "A phase II study of RO4929097 in metastatic colorectal cancer" 48 : 997-1003, 2012

      112 Wheatley-Price P, "A phase II study of PF-03446962 in patients with advanced malignant pleural mesothelioma. CCTG Trial IND. 207" 11 : 2018-2021, 2016

      113 Brandes AA, "A phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma" 18 : 1146-1156, 2016

      114 Goff LW, "A phase I study of the anti-activin receptor-like kinase 1(ALK-1)monoclonal antibody PF-03446962 in patients with advanced solid tumors" 22 : 2146-2154, 2016

      115 Bracken CP, "A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition" 68 : 7846-7854, 2008

      116 Yook JI, "A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells" 8 : 1398-1406, 2006

      117 Vincent T, "A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition" 11 : 943-950, 2009

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