Most hexokinases are widely expressed but distinct hexokinas

Most hexokinases are widely expressed but distinct hexokinases predominate specific tissues (Katzen and Schimke, 1965, Rogers et al., 1975). Hexokinase I is found in all mammalian tissues, but is most abundant in the α-mangostin and kidney (griffin et al., 1992). Hexokinase II is the primary hexokinase in muscle and adipose tissues (Postic et al., 1994). Hexokinase III is mainly present in spleen and lymphocytes (Coerver et al., 1998). GCK, hexokinase IV, is the major hexokinase in the liver and pancreatic tissues (Printz et al., 1993), where it acts as a sensor for changes in circulating glucose levels (Matschinsky et al., 2006). Multiple hexokinase sequences have also been identified in invertebrates such as sea urchin and ascidian (Irwin and Tan, 2008). However, little information is available to date regarding the expression pattern and bioactivity of hexokinases in the invertebrates. Amphioxus or lancelet, a cephalochordate, is the basal extant chordate lineage. It has a vertebrate-like body plan including dorsal neural tube, notochord, liver-like hepatic caecum, and segmented somites, but it is less complex than vertebrates, having a genome uncomplicated by extensive genomic duplication (Putnam et al., 2008). Its genetic sequence information and expression pattern have been widely used for interspecies comparative genome studies and developmental homology analysis (Holland and Holland, 1999, Sun et al., 2010, Wang et al., 2009). In this study, we aimed to identify and characterize the hexokinase gene in the amphioxus Branchiostoma japonicum, named as Bjhk, to examine its expression profile and bioactivity and to explore its phylogenetic relationship to vertebrate hexokinases.
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Acknowledgment This work was supported by the grant of the National Science Foundation of China (31172071).
Introduction Solar UV radiation is the primary cause of skin cancer. Sunlight, especially UVB (range 280–320 nm), acts as a tumor initiator and tumor promoter and is able to damage DNA directly (Madan et al., 2010). Non-melanoma skin cancer, including basal cell carcinoma and cutaneous squamous cell carcinoma (SCC), is the most common form of skin cancer. Actinic keratosis (AK) is on the continuum of transformation from normal skin to SCC and is often referred to as SCC in situ (Röwert-Huber et al., 2007). If untreated, a small fraction of AKs may progress to SCC involving deeper tissues, metastases, and even death (Oppel and Korting, 2004). One of the key characteristics of many types of cancer cells, including SCC cells, is their increased rate of glucose uptake and breakdown (glycolysis). Accordingly, to support their growth and proliferation, their metabolism is often reprogrammed from oxidative phosphorylation to aerobic glycolysis, a phenomenon known as the Warburg effect (Hay, 2016, Lunt and Vander Heiden, 2011). The first step in glycolysis is catalyzed by hexokinases (HKs) that phosphorylate glucose to glucose-6-phosphate. There are four HK isozymes, the most abundant being HK1 and HK2. HK1 is expressed in most normal adult tissue. In contrast, the expression of HK2 under normal conditions is very limited (Wilson, 2003). Moreover, under normal conditions, the subcellular distribution of HK1 and HK2 is different, with HK1 associated mainly with mitochondria and HK2 present primarily in the cytoplasm (John et al., 2011). Unlike the absence or low expression of HK2 in the majority of normal tissue, this enzyme is highly expressed in many cancer types, addressing the greater metabolic demand typical of proliferating cancer cells (Patra et al., 2013, Pedersen et al., 2002). High HK2 levels correlate with poor disease prognosis (Peng et al., 2008, Rho et al., 2007, Smith, 2000) and are required for oncogenic transformation despite possible continuous expression of HK1 (Patra et al., 2013). Both HK1 and HK2 attach to the mitochondria by binding to VDAC1 on the cytosolic side of the outer mitochondrial membrane (Pastorino and Hoek, 2008). The VDAC1 channel allows passage of ions and metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide, and Ca2+, thus enabling the metabolic cross-talk between the mitochondria and the rest of the cell. VDAC1, too, is overexpressed in many cancer types and plays an important role in cancer progression (Shoshan-Barmatz et al., 2015, Shoshan-Barmatz and Mizrachi, 2012).