[Corrigendum] Mutation of TGF‑β receptor II facilitates human bladder cancer progression through altered TGF‑β1 signaling pathway
Copyright policy )[Corrigendum] Mutation of TGF‑β receptor II facilitates human bladder cancer progression through altered TGF‑β1 signaling pathway
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.
- Huazhong University of Science and Technology China (People's Republic of)
- Tongji Hospital China (People's Republic of)
Male, Blotting, Western, Apoptosis, Middle Aged, Protein Serine-Threonine Kinases, Flow Cytometry, Prognosis, Immunoenzyme Techniques, Cell Movement, Mutation, Cell Adhesion, Disease Progression, Humans, Female, RNA, Messenger, Neoplasm Grading, RNA, Small Interfering, Corrigendum, Cell Proliferation, DNA Primers, Neoplasm Staging
Male, Blotting, Western, Apoptosis, Middle Aged, Protein Serine-Threonine Kinases, Flow Cytometry, Prognosis, Immunoenzyme Techniques, Cell Movement, Mutation, Cell Adhesion, Disease Progression, Humans, Female, RNA, Messenger, Neoplasm Grading, RNA, Small Interfering, Corrigendum, Cell Proliferation, DNA Primers, Neoplasm Staging
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