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Journal of Cancer Research and Clinical Oncology

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Open Access 01-04-2019 | Metastasis | Original Article – Cancer Research

Insufficient radiofrequency ablation promotes the metastasis of residual hepatocellular carcinoma cells via upregulating flotillin proteins

Authors: Ning Zhang, Hui Li, Chengdong Qin, Dening Ma, Yiming Zhao, Weiping Zhu, Lu Wang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 4/2019

Abstract

Purpose

Radiofrequency ablation (RFA) therapy has proven to be effective and feasible for early-stage hepatocellular carcinoma (HCC); however, rapid progression of residual tumor cells after RFA has been confirmed, but the molecular mechanisms of this phenomenon are poorly understood. This study evaluated the effect of the lipid raft proteins known as flotillins on the invasive and metastatic potential of residual HCC.

Methods

The human HCC cell line HCCLM3 was used to establish insufficient RFA models in vivo and in vitro. Changes in cellular morphology, soft agar colony formation, motility, metastasis, and epithelial–mesenchymal transition (EMT) markers after insufficient RFA intervention in vitro and in vivo were detected by real-time PCR, western blotting, immunohistochemistry and transwell assays.

Results

The results showed that flotillin-1 and flotillin-2 expression were upregulated in HCCLM3 cells following 45 °C heat treatment and in residual HCCLM3 xenografts cells after insufficient RFA. Knocking down flotillin-1 or flotillin-2 in HCCLM3 cells by shRNA significantly lowered insufficient RFA-induced tumor growth, EMT changes, and metastasis in vitro and in vivo. Furthermore, mechanism studies indicated that flotillins altered the EMT status and metastatic potential of heat-treated HCCLM3 cells by activating the Akt/Wnt/β-catenin signaling pathway.

Conclusions

Our findings present new evidence that flotillins play a key role in the aggressive behaviors of residual cancer cells after insufficient RFA and provide new insights into the regulatory mechanism of Wnt/β-catenin signaling.

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Title: Insufficient radiofrequency ablation promotes the metastasis of residual hepatocellular carcinoma cells via upregulating flotillin proteins
Authors: Ning Zhang
Hui Li
Chengdong Qin
Dening Ma
Yiming Zhao
Weiping Zhu
Lu Wang
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Keywords: Metastasis
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: Journal of Cancer Research and Clinical Oncology / Issue 4/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02852-z

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