Abstract
BackgroundLethal giant larvae (Lgl), scaffolding proteins, regulate the epithelial cell apicobasal polarity in Drosophila. They play important roles in asymmetric cell division, cell migration, and progenitor cells self-renewal as tumor suppressors. One of Lgl mammalian homologues proteins, LLGL2 overexpression has been reported in ER+ breast cancer and promotes tumor proliferation through regulating leucine uptake. Nonetheless, the role of LLGL2 in hepatocellular carcinoma (HCC) is still unknown.MethodsTCGA dataset mining, qRT-PCR, Western blot along with immunohistochemistry assays were employed to explore LLGL2 expression in human HCC samples and cell lines. Moreover, the clinical value of LLGL2 was investigated in 156 HCC patients. Furthermore, the role as well as the molecular mechanism of LLGL2 in the progression of HCC was explored through a series of in vitro and in vivo experiments.ResultsLLGL2 was up-regulated in HCC tissues, which was related with certain clinicopathological features including tumor number, vascular invasion as well as advanced stage. High expression of LLGL2 predicted poor prognosis after hepatectomy. LLGL2 promoted HCC cells proliferation, migration and invasion through PI3K/ATK signaling by promoting calcium ion influx.ConclusionOur study identified that LLGL2 is a tumor promoter in HCC for the first time, which could potentially be utilized as a new biomarker and a therapeutic target for HCC.
Highlights
Hepatocellular carcinoma(HCC) is the 7th leading most frequent cancer as well as the 3rd leading cause of cancer mortalities globally in 2018, and about 841,080 new cases and 781,631 fatalities yearly [1]
The results from this study suggest that LLGL2, the polarity gene, is a potential metastasis promoter of hepatocellular carcinoma (HCC), which may activate PI3K/Akt signaling by increasing intracellular calcium ions
Overexpression of LLGL2 was linked to aggressive clinicopathological characteristics consisting of tumor number, vascular infiltration as well as advanced stage, and it was one of the independent risk indicators of Overall survival (OS) and Disease-free survival (DFS) in HCC
Summary
Hepatocellular carcinoma(HCC) is the 7th leading most frequent cancer as well as the 3rd leading cause of cancer mortalities globally in 2018, and about 841,080 new cases and 781,631 fatalities yearly [1]. Lethal giant larvae (Lgl), one of scaffolding proteins, which is a component of the epithelial apico-basal cell polarity machinery, controls the self-renewal and differentiation properties in progenitor cells acting as a tumor suppressor [9,10,11,12]. It has a vital function in the asymmetric cell division, cell migration and is essential for the development of placental labyrinth layer morphogenesis [21,22,23]. Lethal giant larvae (Lgl), scaffolding proteins, regulate the epithelial cell apicobasal polarity in Drosophila They play important roles in asymmetric cell division, cell migration, and progenitor cells self-renewal as tumor suppressors. One of Lgl mammalian homologues proteins, LLGL2 overexpression has been reported in ER+ breast cancer and promotes tumor proliferation through regulating leucine uptake. The role of LLGL2 in hepatocellular carcinoma (HCC) is still unknown
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