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Enrichment of cancer stem cells via beta-catenin contributing to the tumorigenesis of hepatocellular carcinoma 期刊论文

编号：

a806550d-c33e-4886-bfb3-f7012c2b974c
作者：

Pandit, Harshul#^[1,3]Li, Yan*^[1]Li, Xuanyi^[1];Zhang, Weizhong(张为众)^[2]Li, Suping^[1];Martin, Robert C. G.*^[1,3,4]
语种：

英文
期刊：

BMC CANCER ISSN：1471-2407 2018 年 18 卷 ; AUG 3
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关键词：

Hepatocellular carcinoma Wnt/beta-catenin signaling Cancer stem cells Epithelial cell adhesion molecule (EpCAM) Tumor initiating cells
摘要：

Background: Hepatocellular carcinoma (HCC) is among the deadliest cancers due to its heterogeneity, contributing to chemoresistance and recurrence. Cancer stem-like cells (CSCs) are suggested to play an important role in HCC tumorigenesis. This study investigates the role of Wnt/beta-catenin pathway in CSC enrichment and the capabilities of these CSCs in tumor initiation in orthotopic immunocompetent mouse model.
Methods: HCC-CSCs were enriched using established serum-free culture method. Wnt/beta-catenin pathway activation and its components were analyzed by western blot and qRT-PCR. The role of beta-catenin in enrichment of CSC spheroids was confirmed using siRNA interference. Tumorigenic capabilities were confirmed using orthotopic immunocompetent mouse model by injecting 2 x 10(6) Hepa1-6 CSC spheroids or control cells in upper left liver lobe.
Results: The serum-free cultured Hepa1-6 cells demonstrated self-renewal, spheroid formation, higher EpCAM expression, increased Hoechst-33342 efflux, and upregulated Wnt/beta-catenin signaling. Wnt/beta-catenin pathway upregulation was implicated with the downstream targets, i.e., c-MYC, Cyclin-D1, and LEF1. Also, we found that GSK-3 beta serine-9 phosphorylation increased in Hepa1-6 spheroids. Silencing beta-catenin by siRNA reversed spheroid formation phenotype. Mice injected with Hepa1-6 CSC spheroids showed aggressive tumor initiation and growth compared with mice injected with control cells.
Conclusions: Successfully induced Hepa1-6 spheroids were identified with CSC-like properties. Aberrant beta-catenin upregulation mediated by GSK-3 beta was observed in the Hepa1-6 spheroids. The beta-catenin mediated CSC enrichment in the induced spheroids possesses the capability of tumor initiation in immunocompetent mice. Our study suggests plausible cell dedifferentiation mediated by beta-catenin contributes to CSC-initiated HCC tumor growth in vivo.
推荐引用方式
GB/T 7714：

Pandit Harshul,Li Yan,Li Xuanyi, et al. Enrichment of cancer stem cells via beta-catenin contributing to the tumorigenesis of hepatocellular carcinoma [J].BMC CANCER,2018,18.
APA：

Pandit Harshul,Li Yan,Li Xuanyi,Zhang Weizhong,&Martin Robert C. G..(2018).Enrichment of cancer stem cells via beta-catenin contributing to the tumorigenesis of hepatocellular carcinoma .BMC CANCER,18.
MLA：

Pandit Harshul, et al. "Enrichment of cancer stem cells via beta-catenin contributing to the tumorigenesis of hepatocellular carcinoma" .BMC CANCER 18(2018).
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