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

  • 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
  • View Affiliations

  • 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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November 2013
Volume 43 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Bian, J., Li, B., Zeng, X., Hu, H., Hong, Y., Ouyang, H. ... Shen, G. (2013). Mutation of TGF-β receptor II facilitates human bladder cancer progression through altered TGF-β1 signaling pathway. International Journal of Oncology, 43, 1549-1559. https://doi.org/10.3892/ijo.2013.2065
MLA
Bian, J., Li, B., Zeng, X., Hu, H., Hong, Y., Ouyang, H., Zhang, X., Wang, Z., Zhu, H., Lei, P., Huang, B., Shen, G."Mutation of TGF-β receptor II facilitates human bladder cancer progression through altered TGF-β1 signaling pathway". International Journal of Oncology 43.5 (2013): 1549-1559.
Chicago
Bian, J., Li, B., Zeng, X., Hu, H., Hong, Y., Ouyang, H., Zhang, X., Wang, Z., Zhu, H., Lei, P., Huang, B., Shen, G."Mutation of TGF-β receptor II facilitates human bladder cancer progression through altered TGF-β1 signaling pathway". International Journal of Oncology 43, no. 5 (2013): 1549-1559. https://doi.org/10.3892/ijo.2013.2065