Grb2-associated binder 1 (Gab1) and Gab2 play important roles in cancer cell signaling. In particular, it has been demonstrated that the upregulation of Gab2 may be correlated with the World Health Organization (WHO) grade of gliomas and that patients with high Gab2 expression levels exhibited shorter survival time. However, the prognostic value of combined expression of Gab1 and Gab2 has not been explored. Gab1 and Gab2 expression in human gliomas and non-neoplastic brain tissues was measured by immunohistochemistry. Both the expression levels of Gab1 and Gab2 proteins in glioma tissues were significantly higher than those in non-neoplastic brain tissues (both P < 0.001). In addition, the overexpression of Gab1 and Gab2 proteins were both significantly associated with advanced WHO grades (both P < 0.001) and low KPS (both P = 0.01). Moreover, the overall survival of patients with high Gab1 protein expression or high Gab2 protein expression was obviously lower than those with low expressions (both P < 0.001). Notably, glioma patients with combined overexpression of Gab1 and Gab2 proteins (Gab1-high/Gab2-high) had shortest overall survival (P < 0.001). Furthermore, multivariate analysis showed that Gab1 expression (P = 0.01), Gab2 expression (P = 0.02), and combined expression of Gab1 and Gab2 (Gab1/Gab2, P = 0.006) were all independent prognostic factors for overall survival in glioma patients. Gab1 and Gab2 proteins are differentially expressed in glioma patients and closely correlated with the biological behavior of this malignancy. Combination of Gab1 and Gab2 expression may represent a promising biomarker for prognostication of human gliomas.
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http://dx.doi.org/10.1007/s12032-014-0077-6 | DOI Listing |
Cancers (Basel)
August 2023
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-40530 Gothenburg, Sweden.
Aberrant activation of anaplastic lymphoma kinase (ALK) by activating point mutation or amplification drives 5-12% of neuroblastoma (NB). Previous work has identified the involvement of the insulin-like growth factor 1 receptor (IGF1R) receptor tyrosine kinase (RTK) in a wide range of cancers. We show here that many NB cell lines exhibit IGF1R activity, and that IGF1R inhibition led to decreased cell proliferation to varying degrees in ALK-driven NB cells.
View Article and Find Full Text PDFJ Cell Biol
August 2022
Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL.
Protein tyrosine phosphatases (PTPases) are critical mediators of dynamic cell signaling. A tool capable of identifying transient signaling events downstream of PTPases is essential to understand phosphatase function on a physiological time scale. We report a broadly applicable protein engineering method for allosteric regulation of PTPases.
View Article and Find Full Text PDFJ Cell Commun Signal
March 2021
Molecular Biology and Genetics Department, Tokat Gaziosmanpasa University, 60250, Tokat, Turkey.
Ovarian cancer is the most lethal gynecological malignancy and molecular mechanisms of its progression and metastasis are not completely understood. Some members of GAB (GRB2-associated binding) protein family have been reported to be involved in tumor cell proliferation and metastasis in various cancer types. In the present study, we analyzed the expression of GAB proteins (GAB1, GAB2 and GAB3) in ovarian cancer compared to normal ovarian tissue, in terms of tumor stage, tumor grade and histological type.
View Article and Find Full Text PDFGlia
November 2017
Department of Physiology, Peripheral Neuropathy Research Center (PNRC), College of Medicine, Dong-A University, Busan, South Korea.
The sequential reactive changes in Schwann cell phenotypes in transected peripheral nerves, including dedifferentiation, proliferation and migration, are essential for nerve repair. Even though the injury-induced migratory and proliferative behaviors of Schwann cells resemble epithelial and mesenchymal transition (EMT) in tumors, the molecular mechanisms underlying this phenotypic change of Schwann cells are still unclear. Here we show that the reactive Schwann cells exhibit migratory features dependent on the expression of a scaffolding oncoprotein Grb2-associated binder-2 (Gab2), which was transcriptionally induced by neuregulin 1-ErbB2 signaling following nerve injury.
View Article and Find Full Text PDFJ Biol Chem
August 2017
From the Department of Pathology and Pathophysiology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, China. Electronic address:
M2-polarized macrophages, also known as alternatively activated macrophages, have long been associated with pulmonary fibrosis; however, the mechanism has not been fully defined. Gab1 and Gab2 proteins belong to the Gab family of adaptors and are integral components of the signal specificity in response to various extracellular stimuli. In this report, we found that levels of both Gab1 and Gab2 were elevated in M2-polarized macrophages isolated from bleomycin-induced fibrotic lungs.
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