Abstract
Lymphocyte‐specific protein 1 (LSP1) has been reported to regulate cell biology in several human cancers including lymphoma and breast cancer. However, the functions of LSP1 in human hepatocellular carcinoma (HCC) are still unknown. In this study, we found that LSP1 expression was downregulated in HCC tissues and cell lines, and lower LSP1 expression was correlated with poor clinicopathological features including large tumor size, high Edmondson–Steiner grading and advanced tumor–node–metastasis (TNM) stage. Additionally, we demonstrated that patients with high LSP1 expression had significantly better overall survival and disease‐free survival. Moreover, LSP1 was found to be an independent factor for predicting the prognosis of HCC patients. In vitro and in vivo assays showed that overexpressing LSP1 inhibited HCC growth by inducing both apoptosis and growth arrest. Mechanistically, we found that expression of phosphorylated extracellular regulated protein kinases 1 and 2 (ERK1/2) was downregulated after LSP1 overexpression, indicating LSP1 could suppress HCC growth by inhibiting the ERK pathway in HCC cells. Taken together, these results indicate that LSP1 may serve as a prognostic marker and a potential therapeutic target in human HCC.
Highlights
Hepatocellullar carcinoma (HCC) is currently the fifth most frequently diagnosed malignant tumor and the third leading cause of cancer-related deaths [1]
Previous studies have revealed that Lymphocyte-specific protein 1 (LSP1) was involved in multiple cancers including breast cancer [3], lymphomas [4], Abbreviations Bcl2, B-cell lymphoma 2; CNV, copy number variation; ERK1/2, extracellular regulated protein kinases 1 and 2; HCC, hepatocellular carcinoma; KSR, kinase suppressor of Ras; LSP1, lymphocyte-specific protein 1; MAPK, mitogen-activated protein kinase; tumor–node– metastasis (TNM), tumor–node–metastasis
The results showed that LSP1 was mainly expressed in the cytoplasm (Fig. 1A), and LSP1 was significantly downregulated in HCC tissues compared with adjacent tissues (Fig. 1A, P < 0.001; Fig. 1B, P < 0.05)
Summary
Hepatocellullar carcinoma (HCC) is currently the fifth most frequently diagnosed malignant tumor and the third leading cause of cancer-related deaths [1]. Previous studies have revealed that LSP1 was involved in multiple cancers including breast cancer [3], lymphomas [4], Abbreviations Bcl, B-cell lymphoma 2; CNV, copy number variation; ERK1/2, extracellular regulated protein kinases 1 and 2; HCC, hepatocellular carcinoma; KSR, kinase suppressor of Ras; LSP1, lymphocyte-specific protein 1; MAPK, mitogen-activated protein kinase; TNM, tumor–node–metastasis. LSP1 inhibits the growth of HCC pancreatic cancer [5] and dermatofibroma [6]. We demonstrated that LSP1 was downregulated in human HCC and was an independent prognostic factor for predicting both the overall and the disease-free 5-year survival of HCC patients. LSP1 was inversely related to phosphorylated extracellular regulated protein kinases 1 and 2 (ERK1/2) protein expression in HCC cell lines. Our results suggested that LSP1 inhibited HCC growth by suppressing the ERK1/2 pathway
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