Abstract
BackgroundLIM and SH3 protein 1 (LASP1) is upregulated in several types of human cancer and implicated in cancer progression. However, the expression and intrinsic function of LASP1 in glioblastoma (GBM) remains unclear.MethodOncomine and The Cancer Genome Atlas (TCGA) database was analyzed for the expression and clinical significance of LASP1 in GBM. LASP1 mRNA and protein level were measured by qRT-PCR and western blotting. The effect of LASP1 on GBM proliferation was examined by MTT assay and colony formation assay, the effect of LASP1 on sensitivity of Temozolomide was measured by flow cytometry and subcutaneous tumor model. The association between LASP1 and PI3K/AKT signaling was assessed by western blotting.ResultsOncomine GBM dataset analysis indicated LASP1 is significantly upregulated in GBM tissues compared to normal tissues. GBM dataset from The Cancer Genome Atlas (TCGA) revealed that high LASP1 expression is related to poor overall survival. LASP1 mRNA and protein in clinical specimens and tumor cell lines are frequently overexpressed. LASP1 knockdown dramatically suppressed U87 and U251 cell proliferation. Silencing LASP1 potentiated cell chemosensitivity to temozolomide in vitro, LASP1 knockdown inhibited tumor growth and enhanced the therapeutic effect of temozolomide in vivo. TCGA dataset analysis indicated LASP1 was correlated with PI3K/AKT signaling pathway, and LASP1 deletion inhibited this pathway. Combination treatment with PI3K/AKT pathway inhibitor LY294002 dramatically accelerated the suppression effect of temozolomide.ConclusionLASP1 may function as an oncogene in GBM and regulate cell proliferation and chemosensitivity in a PI3K/AKT-dependent mechanism. Thus, the LASP1/PI3K/AKT axis is a promising target and therapeutic strategy for GBM treatment.
Highlights
LIM and SRC homology region 3 (SH3) protein 1 (LASP1) is upregulated in several types of human cancer and implicated in cancer progression
GBM dataset from The Cancer Genome Atlas (TCGA) revealed that high LIM and SH3 protein 1 (LASP1) expression is related to poor overall survival
TCGA dataset analysis indicated LASP1 was correlated with PI3K/AKT signaling pathway, and LASP1 deletion inhibited this pathway
Summary
LIM and SH3 protein 1 (LASP1) is upregulated in several types of human cancer and implicated in cancer progression. The expression and intrinsic function of LASP1 in glioblastoma (GBM) remains unclear. Glioblastoma (GBM) is the most aggressive type of brain tumor and originates in the parenchyma. The poor survival is due to Recently, LIM and SH3 domain-containing proteins were reported to be upregulated in tumors and associated with a wide spectrum of cellular processes such as proliferation, migration, tumorigenesis, and chemoresistance [4, 5]. Bioinformatics analysis showed LASP1 is upregulated in glioblastoma and related to poor overall survival, but the complex function and molecular mechanism of LASP1 in GBM remains largely unknown
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