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Received Feb 21, 2018; Accepted Apr 10, 2018
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1. Introduction
Hepatocellular carcinoma (HCC) is a highly malignant solid tumor which results in chronic inflammation in the liver [1]. Until now, there is no effective drug for the treatment with advanced HCC patients [2]. The principal character of HCC is early metastasis and poor prognosis. A series of changes in the tumor microenvironment (TME) are involved in the progression of HCC [3]. The adaptation of cancer cells to its surrounding microenvironment depends on the interaction between the extracellular matrix (ECM) with membrane receptors [4]. Many molecules in TME have been reported to influence tumor development by regulating tumor cell proliferation, apoptosis, and motility [5–7]. It has been shown that integrin receptors and its downstream signal molecules, including Src, FAK, and p130Cas, have a remarkable influence on tumor progression and metastasis [8].
Integrins are heterodimeric integral membrane glycoproteins composed of noncovalently associated α- and β-subunits forming 24 heterodimers that recognize distinct but overlapping ligands, which can mediate cell adhesion, migration, and proliferation [9–11]. Different integrins are involved in different cellular processes, such as cell attachment to ECM, cell proliferation, and cell motility, which can be used as therapeutic targets in cancer [12].
Integrin α9 subunit, which pairs only with integrin β1 subunit, mediates the binding to a large number of ECM components to affect cell adhesion and motility. There is a key role of integrin α9β1 in lymphangiogenesis and angiogenesis [13, 14]. Integrin α9β1 is expressed not only by several human normal cells but also by different kinds of human cancer cells and closely correlated with tumor grade [15, 16]. It has been reported that integrin α9β1 in colon carcinoma is linked to tumor cell proliferation and migration by enhanced epithelial-mesenchymal transition (EMT) [17].
However, the biological functions of ITGA9 in HCC and the underlying molecular mechanisms have not been studied yet, therefore placing the restrictions on developing novel anticancer-targeted therapies. In this study, we investigated the role of ITGA9 in HCC and the...