Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC) remains disastrous. Cancer stem cells (CSCs) may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2) is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2？ cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability. 1. Introduction Hepatocellular carcinoma (HCC) is the fifth common cancer in men and the seventh common in women worldwide. Due to its extremely poor prognosis, the deaths and newly diagnosed cases each year are almost equal [1]. Currently, therapeutic strategies for HCC are developing; however, potential curative methods remain surgical resection, transplantation, and radiofrequency ablation [2]. However, according to the widely accepted Barcelona Clinic Liver Cancer (BCLC) staging system, those curative methods are generally limited to early-stage HCC patients, whereas more patients are found with intermediate or advanced stage tumors when diagnosed, thus are not eligible for curative treatment [3]. The effectiveness of noncurative therapies including transcatheter arterial chemoembolization (TACE) and Sorafenib are unsatisfactory, which can only improve overall survival by several months [4]. The dilemma of HCC treatment is largely contributed by the highly malignant behavior of HCC, including early intrahepatic/systemic metastasis and multidrug resistance. The theory of cancer stem cells (CSCs) is proposed in recent years.
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