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Cancer Lett. 2019 Aug 10;457:98-109. doi: 10.1016/j.canlet.2019.05.010. Epub 2019 May 14.

The ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, EMT and cancer stemness in hepatocellular carcinoma.

Author information

1
Department of Surgery, The Chinese University of Hong Kong, Hong Kong; School of Biomedical Sciences, The University of Hong Kong, Hong Kong; Department of Surgery, The University of Hong Kong, Hong Kong.
2
Department of Surgery, The Chinese University of Hong Kong, Hong Kong; Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen and German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Department of Surgery, The Chinese University of Hong Kong, Hong Kong; Department of Surgery, The University of Hong Kong, Hong Kong; RIKEN Center for Life Science Technologies (Division of Genomic Technologies), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
4
Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
5
Department of Surgery, The University of Hong Kong, Hong Kong.
6
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
7
School of Biomedical Sciences, The University of Hong Kong, Hong Kong.
8
Department of Clinical Oncology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong.
9
Department of Surgery, The Chinese University of Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong. Electronic address: stcheung@surgery.cuhk.edu.hk.

Abstract

ATP-binding cassette (ABC) transporters mediate multidrug resistance and cancer stem cell properties in various model systems. Yet, their biological significance in cancers, especially in hepatocellular carcinoma (HCC), remains unclear. In this study, we investigated the function of ABCF1 in HCC and explored its potential as a therapeutic target. ABCF1 was highly expressed in fetal mouse livers but not in normal adult livers. ABCF1 expression was upregulated in HCCs. These results demonstrate that ABCF1 functions as a hepatic oncofetal protein. We further demonstrated elevated ABCF1 expression in HCC cells upon acquiring chemoresistance. Suppression of ABCF1 by siRNA sensitized both parental cells and chemoresistant cells to chemotherapeutic agents. Reversely, ABCF1 overexpression promoted chemoresistance and drug efflux. In addition, overexpression of ABCF1 enhanced migration, spheroid and colony formation and epithelial-mesenchymal transition (EMT) induction. RNA sequencing analysis revealed EMT inducers HIF1α/IL8 and Sox4 as potential mediators for the oncogenic effect of ABCF1 in HCC progression. Together, this study illustrates that ABCF1 is a novel potential therapeutic target for HCC treatment.

KEYWORDS:

Cancer stemness; Drug transporter; HCC; Multidrug resistance; Plasticity

PMID:
31100412
DOI:
10.1016/j.canlet.2019.05.010
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