Acquired Substrate Preference for GAB1 Protein Bestows Transforming Activity to ERBB2 Kinase Lung Cancer Mutants

Fan, Yi; Wong, Lily; Marino, Michael; Ou, Wu; Shen, Yi; Wu, Wen Jin; Wong, Kwok‐Kin; Reiser, Jakob; Johnson, Gibbes R.

doi:10.1074/jbc.m112.434217

Cited by 6 publications

(6 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study for the first time identified GAB1 as a target of miR‐409‐3p in CRC and revealed its unique function in CRC cell migration and invasion, suggesting an important role of abnormal GAB1 expression in CRC progression. Therefore, in addition to post‐translational regulation of GAB1 by phosphorylation, the study by Mraz et al . and our study indicate that the post‐transcriptional regulation of GAB1 expression, for example, by miRNA, might be a novel mechanism by which GAB1 regulates cancer progression.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐409‐3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression

Bai

Weng

Dong

et al. 2015

Intl Journal of Cancer

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most common cancers worldwide and its metastasis accounts for the majority of deaths. However, the molecular mechanisms underlying CRC progression are not well characterized. In this study, we identified miR-409-3p as a tumor suppressor of CRC. MiR-409-3p expression was significantly downregulated in CRC tissue compared to adjacent non-tumor tissue, and reduced miR-409-3p expression was correlated with CRC metastasis. In vitro and in vivo studies revealed that miR-409-3p negatively regulated CRC metastatic capacities, including suppressing cancer cell migration, invasion and metastasis. To explore the mechanism of action of miR-409-3p, we adopted a pathway and pathophysiological event-based target screening and validation approach, and found nine known metastasis-related genes as potential targets. The 3'-UTR binding assays between the candidates and miR-409-3p suggested that only GAB1, NR4A2 and LMO4 were directly regulated by the miRNA. However, endogenous expression analysis revealed that only GAB1 was modulated by miR-409-3p in CRC cells at both the mRNA and protein levels. Furthermore, we provided evidence to conclude that GAB1 was partially responsible for miR-409-3p-mediated metastasis. Taken together, our data demonstrate that miR-409-3p is a metastatic suppressor, and post-transcriptional inhibition of the oncoprotein GAB1 is one of the mechanisms of action of this miRNA. Our finding suggests miR-409-3p might be a novel target for CRC metastasis treatment.Colorectal cancer (CRC) is the third most common cancer in men (746,000 cases, 10.0% of the total) and the second in women (614,000 cases, 9.2% of the total) worldwide.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA‐409‐3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression

Bai

Weng

Dong

et al. 2015

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…GAB1 (Grb2‐associated binding protein‐1) belongs to a family of docking proteins (GAB1, GAB2, GAB3), that when phosphorylated are involved in mediating signal transduction of RTK pathways 28,29 . Preclinical data has shown that GAB1 expression in carcinomas is required for EGF receptor signaling through MAPK and AKT signaling and may play a role in carcinogenesis 30,31 . ABL (Abelson murine leukemia) family proteins, including ABL1 (chr 9q34) and ABL2 (chr 1q25) are proto‐oncogenes that code for ubiquitously expressed tyrosine kinases, which play an important role in cellular division, differentiation, survival/death, and migration 32 .…”

Section: Discussionmentioning

confidence: 99%

“…28,29 Preclinical data has shown that GAB1 expression in carcinomas is required for EGF receptor signaling through MAPK and AKT signaling and may play a role in carcinogenesis. 30,31 ABL (Abelson murine leukemia) family proteins, including ABL1 (chr 9q34) and ABL2 (chr 1q25) are proto-oncogenes that code for ubiquitously expressed tyrosine kinases, which play an important role in cellular division, differentiation, survival/death, and migration. 32 Abnormal constitutive activation of ABL activity through development of fusion proteins has been shown to play a role in human cancer, including BCR-ABL, ETV6-ABL, EML1-ABL, among others.…”

Section: Casementioning

confidence: 99%

GAB1‐ABL1 fusions in tumors that have histologic overlap with NTRK‐rearranged spindle cell tumors

Choo

Rakheja

Davis

et al. 2021

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Fibroblastic spindle cell tumors are a heterogeneous group of rare soft tissue tumors that are increasingly recognized as associated with a variety of kinase gene fusions. We report two cases of GAB1‐ABL1 fusions in spindle cell tumors that histologically overlap with neurotrophic tyrosine receptor kinase (NTRK)‐rearranged spindle cell tumors. The first case occurred in a 76‐year‐old female who had a large deep‐seated spindle cell tumor composed of monotonous ovoid to spindle cells in a background of thick stromal collagen bands with prominent hyalinized vessels and inconspicuous mitoses (<1/10 HPF). Immunohistochemical stains showed co‐expression of S100 and CD34. A GAB1‐ABL1 fusion was detected by whole transcriptome RNA sequencing. The patient had a partial response to imatinib. The second case was previously described as a solitary fibrous tumor, occurring in a 9‐year‐old female with a cellular spindle cell tumor with patchy CD34 immunoexpression but no expression of S100. Upon clinicopathologic re‐review, including anchored multiplex next‐generation sequencing, a GAB1‐ABL1 fusion was identified. In summary, we report the first two cases of spindle cell tumors with variable expression of CD34 and/or S100, driven by GAB1‐ABL1 gene fusions with histologic overlap with NTRK‐rearranged spindle cell tumors, suggesting that ABL‐fusions may also be oncogenic drivers within this spectrum of tumors. These cases highlight the evolving understanding of fibroblastic spindle cell tumor biology and the utility of sequencing in identifying a targetable alteration.

show abstract

“…Briefly, keratinocytes were isolated from skin of 1- to 3-d-old mice, pooled, and maintained in Ca 2+ -free minimal essential medium supplemented with 8% chelexed fetal bovine serum, 0.05 mM Ca 2+ , and penicillin/streptomycin. The pSLIK-Neo/TRE Pitt lentiviral vector plasmids encoding V5-tagged Ras and dominant-negative (S17N) Ras and lentivirus were generated as described previously (Fan et al , 2013). Primary keratinocytes were transduced by lentivirus, and the following day, expression was induced overnight with 20 ng/ml doxycycline (cat.…”

Section: Methodsmentioning

confidence: 99%

“…GTX627408; 1:1000; GeneTex) were used for Western blotting. Western blotting was performed as previously described (Fan et al , 2013).…”

Section: Methodsmentioning

confidence: 99%

Suppression of Wnt/β-catenin signaling by EGF receptor is required for hair follicle development

Tripurani

Wang

Fan

et al. 2018

MBoC

Self Cite

View full text Add to dashboard Cite

Mice that lack the epidermal growth factor receptor (EGFR) fail to develop a hair coat, but the mechanism responsible for this deficit is not completely understood. Here, we show that EGFR plays a critical role to attenuate wingless-type MMTV integration site family member (Wnt)/β-catenin signaling during postnatal hair follicle development. Genetic ablation of EGFR in mice resulted in increased mitotic activity in matrix cells, apoptosis in hair follicles, and impaired differentiation of epithelial lineages that form hair. EGFR is activated in wild-type hair follicle stem cells marked with SOX9 or NFATc1 and is essential to restrain proliferation and support stem cell numbers and their quiescence. We observed elevated levels of Wnt4, 6, 7b, 10a, 10b, and 16 transcripts and hyperactivation of the β-catenin pathway in EGFR knockout follicles. Using primary keratinocytes, we linked ligand-induced EGFR activation to suppression of nascent mRNA synthesis of Wnt genes. Overexpression of the Wnt antagonist sFRP1 in mice lacking EGFR demonstrated that elevated Wnts are a major cause for the hair follicle defects. Colocalization of transforming growth factor α and Wnts regulated by EGFR in stem cells and progeny indicates that EGFR autocrine loops control Wnts. Our findings define a novel mechanism that integrates EGFR and Wnt/β-catenin pathways to coordinate the delicate balance between proliferation and differentiation during development.

show abstract

Acquired Substrate Preference for GAB1 Protein Bestows Transforming Activity to ERBB2 Kinase Lung Cancer Mutants

Cited by 6 publications

References 50 publications

MicroRNA‐409‐3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression

MicroRNA‐409‐3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression

GAB1‐ABL1 fusions in tumors that have histologic overlap with NTRK‐rearranged spindle cell tumors

Suppression of Wnt/β-catenin signaling by EGF receptor is required for hair follicle development

Contact Info

Product

Resources

About