Tonghan Zhang1, Lizhong Liang2, Xiaoling Liu3, Ji-Nan Wu1, Jueyao Chen1, Kui Su1, Qiaoyi Zheng1, Hongzhang Huang4, Gui-Qing Liao4. 1. Department of Oral and Maxillofacial Surgery, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China. 2. Department of Oral and Maxillofacial Surgery, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China. 3. Department of Medicine Intensive Care Unit, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China. 4. Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
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. MATERIALS AND 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.
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. MATERIALS AND 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: Li-Sha Wu; Xiao-Wei Wang; Wen He; Xiao-Ting Ma; Hai-Yue Wang; Mei Han; Bing-Hui Li Journal: J Int Med Res Date: 2019-01-09 Impact factor: 1.671