The Insulin-Like Growth Factor Receptor I Promotes Motility and Invasion of Bladder Cancer Cells through Akt- and Mitogen-Activated Protein Kinase-Dependent Activation of Paxillin

Metalli, David; Lovat, Francesca; Tripodi, Farida; Genua, Marco; Xu, Shi Qiong; Spinelli, Michela; Alberghina, Lilia; Vanoni, Marco; Baffa, Raffaele; Gomella, Leonard G.; Iozzo, Renato V.; Morrione, Andrea

doi:10.2353/ajpath.2010.090904

Cited by 86 publications

(106 citation statements)

References 39 publications

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“…[11][12][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.…”

Section: Insulin and Insulin-like Growth Factors (Igfsmentioning

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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Section: Insulin and Insulin-like Growth Factors (Igfsmentioning

confidence: 99%

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Capoluongo¹

2011

The American Journal of Pathology

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“…We have recently discovered that the IGF-IR is overexpressed in invasive bladder cancer, where it functions as a "scat-ter factor" and promotes motility and invasion without affecting cell proliferation (19). These effects require the activation of Akt and MAPK pathways, and the binding of IGF-I to IGF-IR induces Akt-and MAPK-dependent phosphorylation of paxillin, which is necessary for promoting motility (19).…”

mentioning

confidence: 99%

“…These effects require the activation of Akt and MAPK pathways, and the binding of IGF-I to IGF-IR induces Akt-and MAPK-dependent phosphorylation of paxillin, which is necessary for promoting motility (19). Thus, the IGF-IR may play a critical role in promoting the transition to an invasive and possibly metastatic stage of bladder cancer (19).…”

mentioning

confidence: 99%

Decorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling

Iozzo

Buraschi

Genua

et al. 2011

Journal of Biological Chemistry

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136

170

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“…A previous study (24) and our data suggest that IGF-1R is upregulated in bladder cancer cells. To investigate the possibility of IGF-1R as a biomarker for prognosis, we employed the largest TCGA bladder cancer database.…”

Section: Expression Of Igf-1r Negatively Correlates With Patient Survmentioning

confidence: 59%

miR-143 inhibits bladder cancer cell proliferation and enhances their sensitivity to gemcitabine by repressing IGF-1R signaling

Wang

Niu

et al. 2016

Oncology Letters

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The Insulin-Like Growth Factor Receptor I Promotes Motility and Invasion of Bladder Cancer Cells through Akt- and Mitogen-Activated Protein Kinase-Dependent Activation of Paxillin

Cited by 86 publications

References 39 publications

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Decorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling

miR-143 inhibits bladder cancer cell proliferation and enhances their sensitivity to gemcitabine by repressing IGF-1R signaling

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