Mutation of TGF-Œ≤ receptor II facilitates human bladder cancer progression through altered TGF-Œ≤1 signaling pathway
Authors: Hui Ouyang
Heyu Hu
Bo Li
Huifen Zhu
Zhihua Wang
Ping Lei
Bo Huang
Xiaoyong Zeng
Xiaoxue Zhang
Guanxin Shen
Yi Hong
Jing Bian
Journal: International Journal of Oncology (2013)
Discipline: CLINICAL MEDICINE
Keywords: TGF-Œ≤ receptors; tumor cells; growth arrest; migration; TGF-Œ≤RII mutations
Affiliations: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Abstract:  Tumor cells commonly adapt survival strategies by downregulation or mutational inactivation of TGF-Œ≤ receptors thereby reversing TGF-Œ≤1-mediated growth arrest. However, TGF-Œ≤1-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-Œ≤RII was overexpressed in the bladder cancer cell line T24, concomitant with point mutations, especially the Glu269 to Lys mutation (G ‚Ü?A). Whilst leaving Smad2/3 binding unaffected, TGF-Œ≤RII mutations resulted in the unaffected tumor cell growth and also enhanced cell mobility by TGF-Œ≤1 engagement. Such phenomena are perhaps partially explained by the mutated TGF-Œ≤RII 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-Œ≤RII-Fc vectors or smad2/3 siRNA blocked such abnormal gene expressions. Clinically, such G ‚Ü?A mutations were also found in 18 patients (n=46) with bladder cancer. Comparing the clinical and pathologic characteristics, the pathologic T category (œá2 trend = 7.404, P&lt;0.01) and tumor grade (œá2 trend = 9.127, P&lt;0.01) tended to increase in the G ‚Ü?A mutated group (TGF-Œ≤RII point-mutated group). These findings provide new insights into how TGF-Œ≤1 signaling is tailored during tumorigenesis and new information into the current TGF-Œ≤1-based therapeutic strategies, especially in bladder cancer patient treatment. 

Retracted: No

PubPeer comments:
 Figure 1B, right column * Red boxes: the MCF-7 and T24 panels look very similar * Blue boxes: the A549 and ScaBER panels look very similar  , 
 Corrigendum, 14 December 2020: https: www.spandidos-publications.com 10.3892 ijo.2020.5161  *Subsequently to the publication of the above article, an interested reader drew to the authors attention that, in Fig. 1B on p. 1552, the MCF-7 and T24, and the A549 and ScaBER data panels, respectively, appeared to be strikingly similar. After having re-examined the original data, the authors have realized that these pairings of data panels were indeed duplicates of each other. Essentially, errors were made in the labelling of the data panels pertaining to the separate experiments, and in the compilation of the published version of Fig. 1. The authors, however, were willing to repeat the affected experiments, and obtained results that were consistent with those of the experiments that had been originally performed.* *Consequently, the revised version of Fig. 1 is shown below, showing the new data for Fig. 1B. The results from the flow cytometric analysis demonstrated the abnormally high expression level of TGF-u03b2 receptor II in T24 cells. The authors confirm that these data support the main conclusions presented in their paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum. They also apologise to the readership for any inconvenience caused.* Why did the authors not provide the actual originals? If they verified that these were indeed duplicates with incorrect labels, why did they not provide the correct ones? Even more worrisome is that the purported new Figure 1B provided in the Corrigendum, **is exactly the same** as the original published version. Nothing has changed. Can the authors check why this has happened?   ,