Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the association of candidate tumour suppressor genes SH3GL2, p16(INK4a), p14(ARF), and p15(INK4b) in the pathogenesis of head and neck squamous cell carcinoma (HNSCC), we studied the deletion, mutation, and methylation of these genes in 61 dysplastic lesions and 94 HNSCC samples. In mild dysplasia, SH3GL2, p16(INK4a), and p14(ARF) showed a higher frequency of overall alterations (60-70%) than in p15(INK4b) (40%). However, in subsequent stages of tumour progression, the alteration frequency of these genes did not change significantly. One novel mutation in common exon 2 of p16(INK4a)/p14(ARF) and three in exon 9 of SH3GL2 were seen. Concordance was seen in the expression of these genes with their molecular alterations. Deletions of INK4A-ARF and p15(INK4b) have a significant poor patient outcome. The alterations of p16(INK4a), p14(ARF), and p15(INK4b) were positively correlated with tobacco and inversely with HPV, while SH3GL2 alterations were independent of these factors. Based on aetiological factors, four tumour subtypes were recognized: HPV(-)tobacco(-) (I), HPV(+)tobacco(-) (II), HPV(-)tobacco(+) (III), and HPV(+)tobacco(+) (IV). Groups III and IV showed a high frequency of p16(INK4a)/p14(ARF)/p15(INK4b) alterations with significant poor patient outcome in comparison to group II. Our findings suggest that deregulation of SH3GL2-associated signalling and p16(INK4a)/p14(ARF)/p15(INK4b)-mediated G1-S/G2-M checkpoints of cell cycle are independent pathways for the development of early dysplastic lesions of the head and neck.
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PMID:SH3GL2 and CDKN2A/2B loci are independently altered in early dysplastic lesions of head and neck: correlation with HPV infection and tobacco habit. 1902 82

SH3GL2 (Src homology 3 (SH3) domain GRB2-like 2) is mainly expressed in the central nervous system and regarded as a tumour suppressor in human glioma. However, the molecular mechanism of the SH3GL2 protein involved in malignant behaviours of human glioma has not been elucidated. In this study, we tried to investigate the role of SH3GL2 in glioma cell migration and invasion and explore its underlined molecular mechanism. Firstly, we discovered that the protein level of SH3GL2 was widely decreased in the human glioma patients, especially in high-grade glioma tissues. Then, we determined the role of SH3GL2 in migration and invasion of glioma cells upon SH3GL2 knocking down and overexpressing. It was showed that knocking down of SH3GL2 promoted the migration and invasion of glioma cells, whereas overexpression of SH3GL2 inhibited them. Further study on molecular mechanism disclosed that silencing of SH3GL2 obviously activated the STAT3 (signal transducer and activator of transcription 3) signalling thereby promoting the expression and secretion of MMP2. On the contrary, overexpression of SH3GL2 had opposite effect. Taken together, the above results suggest that SH3GL2 suppresses migration and invasion behaviours of glioma cells through negatively regulating STAT3/MMP2 signalling and that loss of SH3GL2 may intensify the STAT3/MMP2 signalling thereby contributing to the migration and invasion of glioma cells.
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PMID:Loss of SH3GL2 promotes the migration and invasion behaviours of glioblastoma cells through activating the STAT3/MMP2 signalling. 2847 Sep 49