Abstract:
:Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.
journal_name
Am J Cancer Resjournal_title
American journal of cancer researchauthors
Pradip D,Bouzyk M,Dey N,Leyland-Jones Bsubject
Has Abstractpub_date
2013-04-03 00:00:00pages
173-95issue
2issn
2156-6976journal_volume
3pub_type
杂志文章abstract::RABEX-5 has been studied in various solid tumors, but its role in non-small-cell lung cancer (NSCLC) remains unknown. This study is aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with NSCLC. A total of 120 NSCLC patients...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2015-08-15 00:00:00
abstract::Menin, a protein encoded by the MEN1 gene, suppresses cancers associated with multiple endocrine neoplasia type 1 (MEN1), but promotes the development of a subset of leukemia induced by mixed lineage leukemia (MLL)-derived fusion proteins (MLL-FPs). The crystal structure of menin indicates that it acts as a scaffold p...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2019-08-01 00:00:00
abstract::Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent st...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2018-08-01 00:00:00
abstract::Due to the refractory and partial sensitive treatments to malignant cancers, immunotherapy has increasingly become a hotspot in effective anti-tumor research. However, at present, existing animal models could not accurately describe the interaction between human tissue and tumor cells for preclinical trials. Furthermo...
journal_title:American journal of cancer research
pub_type: 杂志文章,评审
doi:
更新日期:2020-12-01 00:00:00
abstract::Histone modification and chromatin remodeling are important events in response to DNA damage, and Polycomb group (PcG) proteins, catalyzing H3K27 methylation, are involved. However, the biological function and mechanism of PcG in DNA damage are not fully understood. Additionally, downstream effectors in hepatocellular...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2017-09-01 00:00:00
abstract::Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2016-09-01 00:00:00
abstract::The link between high-risk human Papillomavirus (HR-HPV) and other sexually transmitted diseases (STDs) in the risk of developing cervical cancer still unclear. Thus, in this report we investigated the rates of co-infections between HPV and other important non-HPV STDs in different cervical findings using a multiplex ...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2016-06-01 00:00:00
abstract::Different types of cancers exhibit disparate spectra of genomic alterations (germline and/or somatic). These alterations can include single nucleotide variants (SNVs), copy number alterations (CNAs) or structural changes (e.g. gene fusions and chromosomal rearrangements). Identification of those genomic alterations ha...
journal_title:American journal of cancer research
pub_type: 杂志文章,评审
doi:
更新日期:2018-08-01 00:00:00
abstract::Over-activation of SUMOylation is correlated with poor prognosis in multiple myeloma (MM), with the mechanism unclear. Wnt signaling is one of the aberrantly regulated pathways related to cancer tumorigenesis and progression. Whether SUMOylation is involved in regulating the activity of Wnt/β-catenin pathway, however,...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2014-12-15 00:00:00
abstract::Glioblastoma (GBM) is the most frequent brain cancer with poor prognosis and few therapies and urgently requires effective treatments. Na+/K+-ATPase is considered as a target for GBM therapy and development of anticancer drugs. Cardiac glycosides bind the Na+/K+-ATPase α subunit to inhibit enzymatic activity and are p...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2019-06-01 00:00:00
abstract::Glioma is one of the most common, rapidly progressive and fatal brain tumors, and accumulating evidence shows that microRNAs (miRNAs) play important roles in the development of cancers, including glioma. Therapeutic applications of miRNAs in Ras-driven glioma have been proposed; however, their specific functions and m...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2017-04-01 00:00:00
abstract::Cancer is a diverse class of diseases characterized by uncontrolled cell growth with the potential to invade and spread to other parts of the body, and continues to be one of the leading causes of death worldwide. Conventional cancer treatment modalities include antitumor drugs, surgical resection, locally targeted th...
journal_title:American journal of cancer research
pub_type: 杂志文章,评审
doi:
更新日期:2019-08-01 00:00:00
abstract::The aim of this study was to evaluate the role of miR-146a in the drug resistance of chronic myelogenous leukemia (CML) cells (K562/ADM) and to investigate the reversal effect of physcion, a natural compound, on the multidrug-resistance in CML. Our results showed that miR-146a was significantly downregulated in drug-r...
journal_title:American journal of cancer research
pub_type: 杂志文章,收录出版
doi:
更新日期:2016-11-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been used as a powerful targeting therapeutic agent for treatment of lung adenocarcinoma for years. Nevertheless, the efficacy of TKI was hampered by the appearance of acquired TKI-resistance. In the present study, we aimed to search, predic...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2015-06-15 00:00:00
abstract::Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that serves many roles in inflammation and immunity; however, it is also involved in carcinogenesis. This is a review of the clinical and experimental data published on MIF and its role in various types of cancers such as glioblastomas, lung canc...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Chemotherapy resistance is a common problem faced by patients diagnosed with epithelial ovarian cancer (EOC). Currently there are no specific or sensitive clinical biomarkers that maybe implemented to identify chemotherapy resistance and give insight to prognosis. The aim of this study is to investigate the ...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2015-01-15 00:00:00
abstract:BACKGROUND:malignant peritoneal mesothelioma (MPM) is a rare peritoneal mesothelial neoplasm. Ki67 and BCL2 are established prognostic markers in several cancers. High Ki67 expression indicates tumour progression, whilst similar expression of BCL2 retards tumour replication. Traditionally, prognosis in MPM is gauged wi...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2013-08-14 00:00:00
abstract::Circular RNAs (circRNAs) are a series of special closed circular RNA molecules with stability and conservatism. In recent years, advances in high-throughput RNA sequencing technology have led to explosive discovery of circRNAs in different types of species and cells. Moreover, circRNAs can accomplish a remarkable mult...
journal_title:American journal of cancer research
pub_type: 杂志文章,评审
doi:
更新日期:2018-07-01 00:00:00
abstract::Cervical cancer is often associated with hypoxia and many kinds of chemokines. But the relationship and role of hypoxia and Chemokine (C-C motif) ligand 17 (CCL17) in cervical cancer are still unknown. Here, we found that CCL17 was high expressed in cervical cancer. HeLa and SiHa cells could secrete CCL17 in a time-de...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2015-09-15 00:00:00
abstract::Radiation remains an important component of cancer treatment. In addition to inducing tumor cell death through direct cytotoxic effects, radiation can also promote the regression of tumor via augment of immune response. Regulatory T cells (Tregs) are a unique subpopulation of CD4 positive cells, which are characterize...
journal_title:American journal of cancer research
pub_type: 杂志文章,评审
doi:
更新日期:2015-10-15 00:00:00
abstract:BACKGROUND:Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2015-06-15 00:00:00
abstract::Understanding mechanisms of cancer metastasis is crucial for reduction of cancer mortality. Acyl-CoA medium-chain synthetase 3 (ACSM3) is an acyl-CoA synthetase which takes part in the first step of fatty acid metabolism. However, the expression, clinical significance and biological function of ACSM3 remain unknown in...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2017-03-01 00:00:00
abstract::Regulation of the Hippo pathway via phosphorylation of Yorkie (Yki), the Drosophila homolog of human Yes-associated protein 1, is conserved from Drosophila to humans. Overexpression of a non-phosphorylatable form of Yki induces severe overgrowth in adult fly eyes. Here, we show that yki mRNA associates with microsomal...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2017-03-01 00:00:00
abstract::Human Schlafen-5 (SLFN5) is aberrantly involved in tumorigenesis in several types of cancer. However, its implications in breast cancer (BRCA) are unknown. Herein, we demonstrated that SLFN5 expression is negatively associated with the tumour growth of human BRCA using GEO database analysis and clinical sample immunos...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2020-09-01 00:00:00
abstract::MicroRNA-122 (miR-122) has been implicated in tumor development and progression in various types of cancers. However, the biological function and regulatory mechanisms of miR-122 in gastric cancer (GC) remain largely unknown. We aimed to determine the biological role and underlying mechanism of miR-122 in GC. Real tim...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2017-02-01 00:00:00
abstract::Factors within the tissue of breast cancer (BC) may shift the polarization of CD4+ T cells towards Th2 direction. This tendency can promote tumor development and be enhanced by the use of tamoxifen during the treatment. Thus, the patients with low levels of tumor-induced Th2 polarization prior to tamoxifen treatment m...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2015-01-15 00:00:00
abstract::Our previous study showed that 5-aza-2-deoxycytidine (5-aza-dC) could inhibit tumor growth by enhancing the susceptibility of ovarian clear cell carcinoma (OCCC) to paclitaxel through decreasing AKT/mTOR expressions. The objective of the study is to evaluate the antitumor efficacy of everolimus (RAD001) and 5-aza-2-de...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2018-01-01 00:00:00
abstract::Tumor-associated NADH oxidase (tNOX, ENOX2), which belongs to a family of growth-related NADH oxidases, was originally identified as a plasma membrane protein of rat hepatoma and is inhibited or downregulated by several anti-cancer drugs. The objective of this study was to evaluate the anti-tumor effects of tNOX used ...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2019-04-01 00:00:00
abstract::Urokinase plasminogen activator receptor (uPAR) is a GPI anchored cell surface protein that is closely associated with invasion, migration, and metastasis of cancer cells. Many functional extracellular proteins and transmembrane receptors interact with uPAR. However, few studies have examined the association of uPAR w...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2014-11-19 00:00:00
abstract::Epigenetic dysregulation is being increasingly recognized as a hallmark of cancer. Post-translational modifications of histones, in particular, are known to play important roles gene expression alterations in cancer development and progression. Given their key involvement in the various stages of carcinogenesis, histo...
journal_title:American journal of cancer research
pub_type: 杂志文章
doi:
更新日期:2012-01-01 00:00:00