Loading...
Please wait, while we are loading the content...
Similar Documents
Dishevelled1-3 contribute to multidrug resistance in colorectal cancer via activating Wnt/β-catenin signaling.
| Content Provider | Europe PMC |
|---|---|
| Author | Zhang, Kun Li, Minhui Huang, Houyi Li, Linpeng Yang, Jie Feng, Li Gou, Junjie Jiang, Mengju Peng, Liaotian Chen, Linyi Li, Ting Yang, Ping Yang, Yuhan Wang, Yuanyuan Peng, Quekun Dai, Xiaozhen Zhang, Tao |
| Copyright Year | 2017 |
| Abstract | Multidrug resistance is a great obstacle in successful chemotherapy of colorectal cancer. However, the molecular mechanism underlying multidrug resistance is not fully understood. Dishevelled, a pivot in Wnt signaling, has been linked to cancer progression, while its role in chemoresistance remains unclear. Here, we found that Dishevelled1-3 was over-expressed in multidrug-resistant colorectal cancer cells (HCT-8/VCR) compared to their parental cells. Silencing Dishevelled1-3 resensitized HCT-8/VCR cells to multiple drugs including vincristine, 5-fluorouracil and oxaliplatin. Moreover, Dishevelled1-3 increased the protein levels of multidrug resistance protein 1 (P-gp/MDR1), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP), Survivin and Bcl-2 which are correlated with multidrug resistance. shβ-catenin abolished Dishevelled-mediated these protein expressions. Unexpectedly, none of Dishevelled1-3 controlled β-catenin accumulation and nuclear translocation. Furthermore, the nuclear translocations of Dishevelled1-3 were promoted in HCT-8/VCR cells compared to HCT-8. Dishevelled1-3 bound to β-catenin in nucleus, and promoted nuclear complex formation and transcription activity of β-catenin/TCF. Taken together, Dishevelled1-3 contributed to multidrug resistance in colorectal cancer via activating Wnt/β-catenin signaling and inducing the expressions of P-gp, MRP2, BCRP, Survivin and Bcl-2, independently of β-catenin accumulation and nuclear translocation. Silencing Dishevelled1-3 resensitized multidrug-resistant colorectal cancer cells, providing a novel therapeutic target for successful chemotherapy of colorectal cancer. |
| Journal | Oncotarget |
| Volume Number | 8 |
| PubMed Central reference number | PMC5777814 |
| Issue Number | 70 |
| PubMed reference number | 29383202 |
| e-ISSN | 19492553 |
| DOI | 10.18632/oncotarget.23253 |
| Language | English |
| Publisher | Impact Journals LLC |
| Publisher Date | 2017-12-14 |
| Access Restriction | Open |
| Rights License | This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. Copyright: © 2017 Zhang et al. |
| Subject Keyword | multidrug resistance colorectal cancer drug sensitivity dishevelled Wnt/β-catenin |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
