Grb7, a Critical Mediator of EGFR/ErbB Signaling, in Cancer Development and as a Potential Therapeutic Target

Chu, Pei-Yu; Tai, Yuling; Shen, Tang‐Long

doi:10.3390/cells8050435

Cited by 43 publications

(43 citation statements)

References 76 publications

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“…Human growth receptor bound protein 7 (Grb7) is a 532 amino acid long adapter protein implicated in cancer progression and invasion upon interaction with its binding partners comprising various receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (ErbB2/HER2) [ 214 ], ErbB3 and ErbB4 [ 215 ], focal adhesion kinase (FAK) [ 216 ], and platelet-derived growth factor (PDGF) receptors [ 217 ]. The overexpression of these RTKs in many cancer types including breast, gastric, and esophageal cancers have been shown to promote their invasive activity [ 218 ]. The C-terminal Src homology (SH2) motif of Grb7 is required for the upstream binding events leading to the activated signaling pathways.…”

Section: Peptides Derived From Combinatorial Screensmentioning

confidence: 99%

Peptide-Based Strategies for Targeted Tumor Treatment and Imaging

Ayo

Laakkonen

2021

Pharmaceutics

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Cancer is one of the leading causes of death worldwide. The development of cancer-specific diagnostic agents and anticancer toxins would improve patient survival. The current and standard types of medical care for cancer patients, including surgery, radiotherapy, and chemotherapy, are not able to treat all cancers. A new treatment strategy utilizing tumor targeting peptides to selectively deliver drugs or applicable active agents to solid tumors is becoming a promising approach. In this review, we discuss the different tumor-homing peptides discovered through combinatorial library screening, as well as native active peptides. The different structure–function relationship data that have been used to improve the peptide’s activity and conjugation strategies are highlighted.

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Section: Peptides Derived From Combinatorial Screensmentioning

confidence: 99%

Peptide-Based Strategies for Targeted Tumor Treatment and Imaging

Ayo

Laakkonen

2021

Pharmaceutics

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“…Levels of SLC7A5 were highly expressed in HNSCC [31] and are closely related to tumor size and grade, effects which constitute the Xc system in ferroptosis [32] and provide amino acids for promotion of cancer cell growth [33]. EGFR, which affects GSH through the phosphorylation of Akt [34], is related to the later stages, tumor size, invasion, decreased survival rates and poor prognosis of HNSCC [35,36]. Further evidence indicating a role for EGFR has been demonstrated in response to treatment with Cetuximab, an EGFR-targeted drug shown to have survival bene ts for metastatic HNSCC disease [4].…”

Section: Discussionmentioning

confidence: 99%

Prognostic model of head and neck squamous cell carcinoma based on 12 ferroptosis-related genes

Li¹,

Zhang²,

Li³

2021

Preprint

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Background: The purpose of our study is establishing a model based on ferroptosis-related genes predicting the prognosis of patients with head and neck squamous cell carcinoma (HNSCC).Methods: In our study, transcriptome and clinical data of HNSCC patients were from The Cancer Genome Atlas, ferroptosis-related genes and pathways were from Ferroptosis Signatures Database. Differentially expressed genes (DEGs) were screened by comparing tumor and adjacent normal tissues. Functional enrichment analysis of DEGs, protein-protein interaction network and gene mutation examination were applied. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression were used to identified DEGs. The model was constructed by multivariate Cox regression analysis and verified by Kaplan-Meier analysis. The relationship between risk scores and other clinical features was also analyzed. Univariate and multivariate Cox analysis was used to verified the independence of our model. The model was evaluated by receiver operating characteristic analysis and calculation of the area under the curve (AUC). A nomogram model based on risk score, age, gender and TNM stages was constructed.Results: We analyzed data including 500 tumor tissues and 44 adjacent normal tissues and 259 ferroptosis-related genes, then obtained 73 DEGs. Univariate Cox regression analysis screened out 16 genes related to overall survival, and LASSO analysis fingered out 12 of them with prognostic value. A risk score model based on these 12 genes was constructed by multivariate Cox regression analysis. According to the median risk score, patients were divided into high-risk group and low-risk group. The survival rate of high-risk group was significantly lower than that of low-risk group in Kaplan-Meier curve. Risk scores were related to T and grade. Univariate and multivariate Cox analysis showed our model was an independent prognostic factor. The AUC was 0.669. The nomogram showed high accuracy predicting the prognosis of HNSCC patients.Conclusion: Our model based on 12 ferroptosis-related genes performed excellently in predicting the prognosis of HNSCC patients. Ferroptosis-related genes may be promising biomarkers for HNSCC treatment and prognosis.

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“…Paper region, a central GM (Grb/Mig) segment with a pleckstrin homology (PH) domain to bind phospholipids which could recruit GRB7 to the plasma membrane, and a carboxyl-terminal src-homology 2 (SH2) domain involved in the recruitment of host proteins to activated upstream target receptors [1,2]. Consequently, GRB7 has been shown to be involved in regulation of cell proliferation, cell migration and invasion in the case of carcinoma cells, and tumor formation [3][4][5].…”

Section: Researchmentioning

confidence: 99%

“…GRB7 protein expression has been reported in cytoplasm, focal adhesions, stress granules, and the nucleus (reviewed in [2]). Deletion of the SH2 domain of GRB7 ablates the localization of GRB7 in focal contacts [16], and interaction of the PH domain with phospholipid may recruit GRB7 to the cell membrane [17].…”

Section: Researchmentioning

confidence: 99%

The prognostic significance of GRB7 protein expression and localization in human breast and ovarian cancers

et al. 2020

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Objective: To study GRB7 protein expression in normal human tissues and breast and ovarian cancers, and determine its clinical significance.Results: GRB7 protein was expressed in multiple tissues, including myoepithelial cells of normal breast and fibroadenoma. Cytoplasmic GRB7 expression was seen predominantly in HER-2 positive and, to a lesser extent, triple negative breast cancer. Membrane localization of GRB7 was present in a subset of breast cancers with high cytoplasmic GRB7 expression. Univariate and multivariate analysis found that cytoplasmic GRB7 expression was associated with a negative progesterone receptor status, while membrane GRB7 expression was associated with a negative axillary nodal status. Membrane associated GRB7 expression was present in a subset of ovarian cancers with high cytoplasmic GRB7 expression. Membrane GRB7 expression displayed a trend towards improved recurrence free survival (RFS). Landmark analysis suggested an RFS advantage for ovarian cancers that had GRB7 membrane expression and survived beyond 27 months; GRB7 membrane expression in two or more cores (out of three) predicted an improved RFS. Membrane expression of GRB7 protein was observed in breast cancer cell lines with high GRB7 protein expression in vitro.Conclusion: GRB7 protein membrane expression may be associated with a better prognosis in breast and ovarian cancers. The favorable prognostic value of GRB7 protein membrane expression and its underlying mechanism is worthy of further investigation.Methods: Immunohistochemistry of normal human tissues, breast tissues of various pathologies, and clinically annotated ovarian cancers was performed to correlate the patterns of GRB7 expression with biomarkers or clinical outcome.

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Grb7, a Critical Mediator of EGFR/ErbB Signaling, in Cancer Development and as a Potential Therapeutic Target

Cited by 43 publications

References 76 publications

Peptide-Based Strategies for Targeted Tumor Treatment and Imaging

Peptide-Based Strategies for Targeted Tumor Treatment and Imaging

Prognostic model of head and neck squamous cell carcinoma based on 12 ferroptosis-related genes

The prognostic significance of GRB7 protein expression and localization in human breast and ovarian cancers

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