Defining the pathway to insulin-like growth factor system targeting in cancer

Rosenzweig, Steven A; Atreya, Hanudatta S.

doi:10.1016/j.bcp.2010.06.013

Cited by 113 publications

(110 citation statements)

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“…Overexpression and activation of IGF-1R have been associated with some different aspects of the progression in cancer (10). Several studies indicate that in breast cancer, both IGF-1 and EGF are involved in the processes of cell adhesion, invasion and anchorage-independent growth that finally lead to the migration and metastatic spreading (19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

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Involvement of the Src-cortactin pathway in migration induced by IGF-1 and EGF in human breast cancer cells

Mezi

Todi

Orsi

et al. 2012

International Journal of Oncology

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Abstract. Cancer cells need to become motile in order to escape the primary tumor and move to distant areas to form metastasis. They move as single cells or as a group, following different stimuli, including growth factors. Among them, insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) and their receptors have been implicated in the development and progression of human breast carcinoma. In this report, we provide evidence that the tyrosine kinase Src is responsible for migration promoted by both IGF-1 and EGF in MDA-MB-231 and MCF7 cells, although with a different effect. Moreover, both IGF-1 and EGF induce reorganization of actin cytoskeleton in lamellipodia and membrane ruffles in a time-and Src-dependent manner. Furthermore, we analyzed the tyrosine phosphorylation status of the actin-binding protein cortactin upon growth factor stimulation, showing that even the activation of cortactin is time-and Src-dependent. In addition, immunofluorescence analysis with anti-paxillin antibody reveals that, after treatment with growth factors, tyrosine phosphorylated cortactin is localized on the plasma membrane in correspondence of focal adhesions. Collectively, our findings suggest a crucial role for Src-mediated activation of cortactin in cell migration, reorganization of actin cytoskeleton and phosphotyrosine cortactin localization to the focal adhesions in human breast cancer cell lines upon both IGF-1 and EGF stimulation.

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Section: Discussionmentioning

confidence: 99%

“…Overexpression and activity of IGF-1R have been associated with many different types of tumors, such as breast, prostate, lung, colon and head and neck squamous cell carcinoma (10). The IGF-1R is overexpressed in estrogen receptor (ER)-positive cells.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the Src-cortactin pathway in migration induced by IGF-1 and EGF in human breast cancer cells

Mezi

Todi

Orsi

et al. 2012

International Journal of Oncology

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“…This explains the broad range of IGF system targeting molecules and strategies still being investigated for the development of more efficient therapies, especially for melanoma. 62 I believe that a better understanding of the complex machinery involved in the regulation of the IGF system in melanomas is required to provide new effective treatment strategies for those conditions in which the IGF system is directly involved.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Capoluongo¹

2011

The American Journal of Pathology

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Insulin and insulin-like growth factors (IGFsMelanoma is a malignant tumor originating from melanocytes, the melanin-producing cells.1,2 During fetal development, melanocytes migrate to different body areas, such as the skin, uvea, leptomeninges, and mucous membranes (eg, upper esophagus, vulva, and anus).2 Although melanoma may arise in all these sites, cutaneous melanoma is by far the most frequent type of melanoma, representing approximately 5% to 7% of all skin malignancies and the most lethal skin cancer (approximately 75% of all deaths from skin tumors).2,3 The following melanoma risk factors have been extensively described: i) sun exposure, ii) presence of dysplastic nevi, iii) age, iv) ethnicity, v) personal or family history of melanoma, vi) phototype, vii) presence of xeroderma pigmentosum, viii) Li-Fraumeni syndrome, ix) hereditary retinoblastoma history, and x) immunosuppressive conditions. 4 In addition to environmental and individual risk factors, the genetic pedigree may also represent a further risk factor for melanoma development; indeed, multiple differences between melanoma cell genomes and those of normal melanocytes were identified in genomewide analysis studies. In particular, point mutations, deletions, gene amplifications and translocations, and/or epigenetic modifications (eg, promoter hypermethylation) appear to be associated with a significant growth advantage, as opposed to normal skin cells. 5 Furthermore, many molecular changes have been reported in advanced stages of melanoma, as opposed to normal melanocytes. The most common mutations are as follows: i) protoncogene serine/threonine kinase B-Raf-activating mutations, 6 ii) E-cadherin expression silencing, 7 and iii) telomerase activity acquisition, 8 followed by hundreds more, identified by comparative gene expression profiling of melanomas with various American Joint Committee on Cancer stages. 1,9,10 A recent article by Bennet 1 provided a detailed list of possible genes involved in melanoma spreading and development.Along with all pathways and molecules studied in different cancers, including melanoma itself, the study of the insulin-like growth factor (IGF) network of ligands, cell surface receptors, and IGF-binding proteins (IGFBPs; eg, the IGF-1 system) have attracted considerable interest because these pathways play important roles at multiple levels, from cellular and organ to organism.11-13 The IGF system mediates growth, differentiation, and developmental processes; it is involved in a variety of metabolic activities.13 Deregulation of IGF system expression and action is linked to several pathological features, ranging from growth deficits to cancer development. TarSupported by the Italian Health Ministry (code ONC_ORD3207) and Programma strategico 3: Diagnostica ad elevata complessità e tecnologie per il monitoraggio di pazienti con patologie croniche-PROGETTO 4_ISS.Accepted for publication August 10, 2010. CME Disclosure: The author did not disclose any relevant financial relationships.Address reprint requests to Ettor...

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“…This creates a rationale to target and deactivate IGF-1R as a potential approach for cancer therapy [6]. Several IGF-1R targeting drugs are under preclinical and clinical development [7,8] where the main strategies to deactivate signalling include receptor blockade, kinase inhibition and ligand sequestration. Currently, IGF-1R blockade by a monoclonal antibody is the most common approach in clinical trials [7].…”

Section: Introductionmentioning

confidence: 99%