title: TGFβ1-Smad3-Jagged1-Notch1-Slug signaling pathway takes part in tumorigenesis and progress of tongue squamous cell carcinoma.
abstract: BACKGROUND
  TGFβ1 and Smad3 play an important role in the process of EMT. TGFβ1 regulates the expression of Jagged1 by modulating Notch signaling. Jagged1 is related to tumor invasion, metastasis, chemotherapy resistance, and tumor immune escape. The aims of this study are to examine deregulation of TGFβ1-Smad3-Jagged1-Notch1-Slug signaling in TSCC and to investigate its roles in TSCC progression.
  
  
  METHODS
  Notch1, Smad3, Jagged1 and Slug proteins and mRNA expression were detected in specimens from 89 cases of patients. We analyzed the correlation between their expressions and histological grade, clinical stage and lymph node metastasis.
  
  
  RESULTS
  Notch1, Smad3, Jagged1 and Slug mRNA expressions in TSCC were higher than normal tissue (P <0.05). The protein expression of Notch1 and Smad3 in TSCC were higher (χ(2) =7.30, P <0.01 and χ(2) = 5.84, P <0.05). Notch1 and Smad3 expressions were correlated with clinical stage (χ(2) =18.81, P<0.01; χ(2) =22.29, P<0.01), but not Jagged1 (χ(2) =0.53, P>0.05). The Slug protein expression was correlated with clinical stage. The positive rate of Notch1 was higher in lymph node metastases positive cases (χ(2) =7.30, P<0.01). Moreover, higher expression of Jagged1 was found in lymph node positive cases (χ(2) =10.82, P<0.01).
  
  
  CONCLUSIONS
  The key protein expression in TGFβ1-Smad3-Jagged1-Notch1-Slug signaling pathway significantly correlated with the clinicopathological features of TSCC patients. It's potential as a biomarker and a novel therapeutic target for TSCC patients at risk of metastasis. It may play an irreplaceable role in TSCC progression which may attribute to promoting EMT which enhances cell migration, invasion and metastasis.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China.
authors.forename: Tonghan
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Medicine Intensive Care Unit, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China.
authors.forename: Ji-Nan
authors.initials: JN
authors.lastname: Wu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China.
authors.forename: Jueyao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Su
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China.
authors.forename: Qiaoyi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Gui-Qing
authors.initials: GQ
authors.lastname: Liao
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D000072100:Jagged-1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051900:Smad3 Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D000072100:Jagged-1 Protein; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; C497790:SMAD3 protein, human; C000604407:SNAI1 protein, human; D051900:Smad3 Protein; D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: EMT; Smad3; TGFβ1; tongue squamous cell carcinoma