Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0029463 (
osteosarcoma
)
16,637
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
An oncogenic role, p21-activated kinase 5 (PAK5), has proven as a significant mediator for many cellular progression, which is expressed highly in human organs such as lung, liver, kidney, blood vessels endothelial cells and inflammatory cells. PAK5 was primitively detected in the cerebrum and accelerated the filopodia formation in neurocytes. It can reverse the effect of Rho and adjust its activity to mediate maintenance and development of nerve axon by binding with Cdc42-
GTP
. Moreover, PAK5 has been suggested to mediate protean, multitudinous and inscrutable functions in cancer. Currently, many researches indicated that PAK5 was dysregulated in ovarian cancer, cervical cancer, melanoma,
osteosarcoma
, renal carcinoma, breast cancer, gastric cancer and so on, which was involved in cell proliferation, apoptosis, migration and invasion. This review focuses the latest knowledge on the structure, expression, signalling pathway of PAK5, emphasizing its function in cancer.
...
PMID:Human p21-activated kinase 5 (PAK5) expression and potential mechanisms in relevant cancers: Basic and clinical perspectives for molecular cancer therapeutics. 3180 88
Osteosarcoma
is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of
osteosarcoma
remain poorly understood. Here we identify exon-intron fusion genes in
osteosarcoma
cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a
1-38
) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of
osteosarcoma
. The Rab22a
1-38
moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a
GTP
-GDP exchange factor of RhoA. This association facilitates the release of
GTP
-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of
osteosarcoma
. Our findings may provide a promising strategy for a subset of
osteosarcoma
patients with lung metastases.
...
PMID:Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma. 3252 25
Background:
Rab22a-NeoF1 fusion gene containing the 1-38aa of Rab22a (Rab22a
1-38
) plays a decisive role in driving tumor metastasis by activating RhoA via binding to SmgGDS607. However, its intercellular regulation remains unknown.
Methods:
The Lys7 (K7) acetylation of Rab22a-NeoF1 was initially identified by mass spectrum. Co-transfection, immunoprecipitation and Western blotting were used to characterize the acetyltransferases and deacetylases responsible for the K7 acetylation of Rab22a-NeoF1, and to define the interaction of proteins. The specificity of K7 acetylation of Rab22a-NeoF1 was determined by its specific anti-K7ac-Rab22a-NeoF1 antibody and its K7R mutant. RhoA-
GTP
was measured by RhoA activation assay. The migration and invasion were assessed by Transwell assay without and with Matrigel matrix, respectively. The orthotopic
osteosarcoma
metastasis model
in vivo
was used to monitor the lung metastases of U2OS/MTX300-Luc stably expressing Vector, Rab22a-NeoF1 or its K7R mutant with or without C646, a relatively specific inhibitor of p300/CBP. The unpaired Student
t
test was used for the statistical significance.
Results:
The K7 of Rab22a-NeoF1 is acetylated by p300/CBP while is de-acetylated by both HDAC6 and SIRT1. The K7R mutant of Rab22a-NeoF1 lacks its binding to SmgGDS607 and subsequently lost its promoting functions, such as activation of RhoA, cell migration, invasion and lung metastasis in
osteosarcoma
in vitro
and
in viv
o, which are also diminished by p300/CBP inhibitor C646.
Conclusion:
The promoting function of Rab22a-NeoF1 is dependent on its K7 acetylation in
osteosarcoma
, and targeting this acetylation (e.g., C646) may benefit cancer patients, in particular
osteosarcoma
patients, who are positive for the Rab22a
1-38
.
...
PMID:Acetylation dependent functions of Rab22a-NeoF1 Fusion Protein in Osteosarcoma. 3268 17
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