Dishevelled1-3 contribute to multidrug resistance in colorectal cancer via activating Wnt/β-catenin signaling.
作者： Kun Zhang , Minhui Li , Houyi Huang , Linpeng Li , Jie Yang
DOI: 10.18632/ONCOTARGET.23253
关键词:
摘要: Multidrug resistance is a great obstacle in successful chemotherapy of colorectal cancer. However, the molecular mechanism underlying multidrug not fully understood. Dishevelled, pivot Wnt signaling, has been linked to cancer progression, while its role chemoresistance remains unclear. Here, we found that Dishevelled1-3 was over-expressed multidrug-resistant cells (HCT-8/VCR) compared their parental cells. Silencing resensitized HCT-8/VCR multiple drugs including vincristine, 5-fluorouracil and oxaliplatin. Moreover, increased protein levels 1 (P-gp/MDR1), resistance-associated 2 (MRP2), breast (BCRP), Survivin Bcl-2 which are correlated with resistance. shβ-catenin abolished Dishevelled-mediated these expressions. Unexpectedly, none controlled β-catenin accumulation nuclear translocation. Furthermore, translocations were promoted HCT-8. bound nucleus, complex formation transcription activity β-catenin/TCF. Taken together, contributed via activating Wnt/β-catenin signaling inducing expressions P-gp, MRP2, BCRP, Bcl-2, independently cells, providing novel therapeutic target for
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