Mutation of TGF-β receptor II facilitates human bladder cancer progression through altered TGF-β1 signaling pathway Corrigendum in /10.3892/ijo.2020.5161

Bian,Jing; Li,Bo; Zeng,Xiaoyong; Hu,Heyu; Hong,Yi; Ouyang,Hui; Zhang,Xiaoxue; Wang,Zhihua; Zhu,Huifen; Lei,Ping; Huang,Bo; Shen,Guanxin

doi:10.3892/ijo.2013.2065

Mutation of TGF-β receptor II facilitates human bladder cancer progression through altered TGF-β1 signaling pathway

Corrigendum in: /10.3892/ijo.2020.5161

Authors:
- Jing Bian
- Bo Li
- Xiaoyong Zeng
- Heyu Hu
- Yi Hong
- Hui Ouyang
- Xiaoxue Zhang
- Zhihua Wang
- Huifen Zhu
- Ping Lei
- Bo Huang
- Guanxin Shen
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Affiliations: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 43003, P.R. China
Published online on: August 20, 2013 https://doi.org/10.3892/ijo.2013.2065
Pages: 1549-1559

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Abstract

Tumor cells commonly adapt survival strategies by downregulation or mutational inactivation of TGF-β receptors thereby reversing TGF-β1-mediated growth arrest. However, TGF-β1-triggered signaling also has a protumor effect through promotion of tumor cell migration. The mechanism(s) through which malignant cells reconcile this conflict by avoiding growth arrest, but strengthening migration remains largely unclear. TGF-βRII was overexpressed in the bladder cancer cell line T24, concomitant with point mutations, especially the Glu269 to Lys mutation (G→A). Whilst leaving Smad2/3 binding unaffected, TGF-βRII mutations resulted in the unaffected tumor cell growth and also enhanced cell mobility by TGF-β1 engagement. Such phenomena are perhaps partially explained by the mutated TGF-βRII pathway deregulating the p15 and Cdc25A genes that are important to cell proliferation and CUTL1 gene relevant to motility. On the other hand, transfecting recombinant TGF-βRII-Fc vectors or smad2/3 siRNA blocked such abnormal gene expressions. Clinically, such G→A mutations were also found in 18 patients (n=46) with bladder cancer. Comparing the clinical and pathologic characteristics, the pathologic T category (χ2 trend = 7.404, P<0.01) and tumor grade (χ2 trend = 9.127, P<0.01) tended to increase in the G→A mutated group (TGF-βRII point-mutated group). These findings provide new insights into how TGF-β1 signaling is tailored during tumorigenesis and new information into the current TGF-β1-based therapeutic strategies, especially in bladder cancer patient treatment.

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