title: Implications of the Notch1-Snail/Slug-epithelial to mesenchymal transition axis for lymph node metastasis in infiltrating ductal carcinoma.
abstract: Emerging evidence suggests that activation of the Notch1 signaling pathway inducing epithelial to mesenchymal transition (EMT) mediated by Snail/Slug promotes invasion and metastasis of breast cancer cells in vitro. However, the implication of the Notch1-Snail/Slug-EMT axis in breast cancer patients remains unclear. A total of 200 formalin-fixed paraffin-embedded samples of invasive ductal carcinoma (IDC), and 37 adjacent non-neoplastic tissue (ANNT) samples from patients who had not been treated with neoadjuvant therapy were examined. Expression of Notch1, Slug, Snail, E-cadherin, N-cadherin, and vimentin was determined by immunohistochemistry on tissue microarrays (TMAs). The correlation between protein expression and clinicopathological characteristics of breast cancer patients was also evaluated. Results showed that a significantly high percentage of cases with high expression of Notch1 (74%, 148/200), Slug (36%, 72/200), Snail (62%, 124/200), and N-cadherin (77%, 153/200) and a low percentage of cases with high expression of E-cadherin (27%, 54/200) were observed in IDC compared to those in ANNTs. High Notch1, Slug, Snail, and N-cadherin expression and low E-cadherin expression in patients with IDC were significantly correlated with lymph node metastasis. In addition, correlation analysis results revealed that high Notch1 expression was significantly associated with high Slug, Snail, and N-cadherin expression and low E-cadherin expression in IDC. Furthermore, a high Snail expression was significantly associated with low E-cadherin expression, and a high Slug expression was found to be significantly associated with increased N-cadherin expression in patients with IDC. Hence, our study suggested that the Notch1-Snail/Slug-EMT axis may be implicated in the lymph node metastasis affecting patients with IDC.
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Yu-Wen
authors: YW
authors: Cao
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Guo-Xing
authors: GX
authors: Wan
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Jian-Ping
authors: JP
authors: Sun
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Xiao-Bin
authors: XB
authors: Cui
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Jian-Ming
authors: JM
authors: Hu
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Wei-Hua
authors: WH
authors: Liang
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Yu-Qin
authors: YQ
authors: Zheng
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors: Wen-Qin
authors: WQ
authors: Li
authors: Department of Pathology and the Key Laboratories for Xinjiang Endemic and Ethnic Diseases (a joint venture with the Chinese Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China. Electronic address: Fengli7855@126.com.
authors: Feng
authors: F
authors: Li
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000556:secondary; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: Epithelial to mesenchymal transition; Invasive ductal carcinoma; Notch1; Slug; Snail
references: J Exp Med. 2007 Nov 26;204(12):2935-48
references: 17984306
references: Genes Dev. 2004 Jan 1;18(1):99-115
references: 14701881
references: Int J Biochem Cell Biol. 2010 Jul;42(7):1115-22
references: 20348013
references: J Transl Med. 2012 Nov 19;10:226
references: 23157797
references: Int J Surg Pathol. 2012 Apr;20(2):139-45
references: 22084425
references: Curr Opin Cell Biol. 2003 Dec;15(6):740-6
references: 14644200
references: Nat Rev Cancer. 2002 Jun;2(6):442-54
references: 12189386
references: Cell. 2009 Nov 25;139(5):871-90
references: 19945376
references: Int J Biochem Cell Biol. 2012 May;44(5):776-89
references: 22330899
references: Clin Exp Metastasis. 2011 Dec;28(8):811-8
references: 21789718
references: Mol Endocrinol. 2008 Sep;22(9):2085-98
references: 18550773
references: Asia Pac J Clin Oncol. 2011 Dec;7(4):385-91
references: 22151989
references: Cancer Cell. 2005 Sep;8(3):197-209
references: 16169465
references: Med Oncol. 2012 Dec;29(5):3240-9
references: 22661383
references: Nat Rev Cancer. 2007 Jun;7(6):415-28
references: 17508028
references: BMC Cancer. 2009 Sep 14;9:325
references: 19751508
references: Breast Cancer Res. 2003;5(2):101-6
references: 12631389
references: J Clin Invest. 2009 Jun;119(6):1438-49
references: 19487820
references: J Cancer Res Clin Oncol. 2013 May;139(5):739-46
references: 23354842
references: Br J Cancer. 2010 Jan 19;102(2):351-60
references: 20010940
references: Nat Med. 2002 Sep;8(9):979-86
references: 12185362
references: Ann Surg Oncol. 2005 Jun;12(6):488-96
references: 15864483
references: J Pathol. 2008 Jan;214(1):25-37
references: 17973239
references: Acta Biochim Biophys Sin (Shanghai). 2008 Jul;40(7):643-50
references: 18604456
references: J Surg Oncol. 2013 Feb;107(2):188-94
references: 22886823
references: Anticancer Res. 2011 Jun;31(6):2389-93
references: 21737670
references: Clin Cancer Res. 2007 Aug 15;13(16):4769-76
references: 17699854
references: Breast Cancer Res Treat. 2014 Jan;143(1):99-111
references: 24305977