The Insulin‐Like Growth Factor System

Roith, Derek Le

doi:10.1155/edr.2003.205

Cited by 165 publications

(106 citation statements)

References 90 publications

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“…Global activation of IGF-IR signaling and loss of negative feedback to IRS-1 appear to be reprogrammed in endometrial hyperplasia (18). IGF1R is overexpressed in the majority of malignant tissues, where it binds IGF to function as an anti-apoptotic agent by enhancing cell survival (19,20). In the present study, downregulation of IRS1 and IGF1R was detected upon ARID1A depletion in HEC-1-A cell lines.…”

Section: Discussionsupporting

confidence: 50%

“…IGF1 and IGF2 are strong mitogens that exert proliferative and anti-apoptotic effects via 2 downstream signaling pathways, the MAPK/ERK and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B cascades (2). The IR, IRS1/2 and MAPK/ERK1/2 signaling pathways have all been revealed to be highly expressed in EC (19,21). Wang et al (21) demonstrated that visfatin stimulated EC cell proliferation by inducing G1/S cycle progression via activation of IR, PI3K/protein kinase B and MAPK/ERK1/2 signaling pathways and consequent upregulation of MYC proto-oncogene, bHLH transcription factor and cyclin D1.…”

Section: Discussionmentioning

confidence: 99%

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Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

et al. 2017

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Abstract. Mutations in the gene encoding AT-rich interactive domain 1A (ARID1A) are frequently observed in endometrial cancer (EC) but the molecular mechanisms linking the genetic changes remain to be fully understood. The present study aimed to elucidate the influence of ARID1A mutations on signaling pathways. Missense, synonymous and nonsense heterozygous ARID1A mutations in the EC HEC-1-A cell line were verified by Sanger sequencing. Mutated ARID1A small interfering RNA was transfected into HEC-1-A cells. Biochemical microarray analysis revealed 13 upregulated pathways, 17 downregulated pathways, 14 significantly affected disease states and functions, 662 upstream and 512 downstream genes in mutated ARID1A-depleted HEC-1-A cells, among which the mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin-like growth factor-1 (IGF1) signaling pathways were the 2 most downregulated pathways. Furthermore, the forkhead box protein O1 pathway was upregulated, while the IGF1 receptor, insulin receptor substrate 1 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit b pathways were downregulated. Carcinoma tumorigenesis, tumor cell mitosis and tumor cell death were significantly upregulated disease states and functions, while cell proliferation and tumor growth were significantly downregulated. The results of the present study suggested that ARID1A may be a potential prognostic and therapeutic molecular drug target for the prevention of EC progression.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

et al. 2017

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“…The insulin-like growth factor (IGF) signaling axis includes two IGF ligands (IGF-1 and IGF-2), two receptors (IGF1R and IGF2R) and at least six binding proteins (IGFBP 1-6) (Le Le Roith and Roberts, 2003;Yakar et al, 2005). Deregulated IGF-1 signaling has been associated with the risk of breast, colon, lung, prostate and other cancers (Pollak et al, 2004;Foulstone et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Enforced epithelial expression of IGF-1 causes hyperplastic prostate growth while negative selection is requisite for spontaneous metastogenesis

et al. 2007

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The insulin-like growth factor-1 (IGF-1) signaling axis is important for cell growth, differentiation and survival and increased serum IGF is a risk factor for prostate and other cancers. To study IGF-1 action on the prostate, we created transgenic (PB-Des) mice that specifically express human IGF-1 des in prostate epithelial cells. This encodes a mature isoform of IGF-1 with decreased affinity for IGF binding proteins (IGFBP) due to a 3-amino acid deletion in the N terminus. Expression of IGF-1 des was sufficient to cause hyperplastic lesions in all mice, however the welldifferentiated lesions did not progress to adenocarcinoma within a year. Remarkably, crossing the PB-Des mice to an established model of prostate cancer delayed progression of organ-confined tumors and emergence of metastatic lesions in young mice. While dissemination of metastatic lesions was widespread in old bigenic mice we did not detect IGF-1 des in poorly differentiated primary tumors or metastatic lesions. Expression of endogenous IGF-1 and levels of P-Akt and P-Erk were reduced independent of age. These data suggest that increased physiologic levels of IGF-1 facilitate the emergence of hyperplastic lesions while imposing a strong IGF-1-dependent differentiation block. Selection against IGF-1 action appears requisite for progression of localized disease and metastogenesis.

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“…Growth hormone (GH) is the major factor stimulating IGF‐I biosynthesis and release, and IGF‐I mediates many, but not all, of its activities 25, 34. The post‐natal growth of bone and muscles depends on pre‐ and post‐pubertal levels of IGF‐I 35.…”

Section: Igfs and Igfbp‐6 Have Multiple Important Functionsmentioning

confidence: 99%

From fever to immunity: A new role for IGFBP‐6?

Liso

Capitanio

Gerli

et al. 2018

J Cellular Molecular Medi

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Fever is a fundamental response to infection and a hallmark of inflammatory disease, which has been conserved and shaped through millions of years of natural selection. Although fever is able to stimulate both innate and adaptive immune responses, the very nature of all the molecular thermosensors, the timing and the detailed mechanisms translating a physical trigger into a fundamental biological response are incompletely understood. Here we discuss the consequence of hyperthermic stress in dendritic cells (DCs), and how the sole physical input is sensed as an alert stimulus triggering a complex transition in a very narrow temporal window. Importantly, we review recent findings demonstrating the significant and specific changes discovered in gene expression and in the metabolic phenotype associated with hyperthermia in DCs. Furthermore, we discuss the results that support a model based on a thermally induced autocrine signalling, which rewires and sets a metabolism checkpoint linked to immune activation of dendritic cells. Importantly, in this context, we highlight the novel regulatory functions discovered for IGFBP‐6 protein: induction of chemotaxis; capacity to increase oxidative burst and degranulation of neutrophils, ability to induce metabolic changes in DCs. Finally, we discuss the role of IGFBP‐6 in autoimmune disease and how novel mechanistic insights could lead to exploit thermal stress‐related mechanisms in the context of cancer therapy.

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The Insulin‐Like Growth Factor System

Cited by 165 publications

References 90 publications

Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT‑rich interactive domain 1A in endometrial cancer

Enforced epithelial expression of IGF-1 causes hyperplastic prostate growth while negative selection is requisite for spontaneous metastogenesis

From fever to immunity: A new role for IGFBP‐6?

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