Cross‐talk between the insulin‐like growth factor (IGF) axis and membrane integrins to regulate cell physiology

Beattie, James; McIntosh, L.P.; Walle, Christopher F. van der

doi:10.1002/jcp.22183

Cited by 31 publications

(28 citation statements)

References 127 publications

(123 reference statements)

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“…Indeed, we previously demonstrated that endothelial cell interaction with denatured collagen, an important αvβ3 ligand expressed selectively within the tumor microenvironment of melanomas, suppresses the expression of IGFBP-4 [37]. IGFBP-4 has been suggested to regulate tumor growth and angiogenesis [37–40, 45]. However, the mechanism by which binding to denatured collagen regulates IGFBP-4 expression is not known.…”

Section: Resultsmentioning

confidence: 99%

“…Given these findings, it is possible that the ECM may contribute to the control of the angiogenic switch. Previous studies suggest that endothelial cell interaction with denatured collagen suppresses expression of IGFBP-4 [37], an important regulator of IGF-1 signaling and angiogenesis [38–40]. However, the mechanisms by which cellular interactions with structurally altered collagen regulates IGFBP-4 is not known.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of tumor-associated αvβ3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo

et al. 2014

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A more complete understanding of the mechanisms that regulate the angiogenic switch, which contributes to the conversion of small dormant tumors to actively growing malignancies, is important for the development of more effective anti-angiogenic strategies for cancer therapy. While significant progress has been made in understanding the complex mechanisms by which integrin αvβ3 expressed in endothelial cells governs angiogenesis, less is known concerning the ability of αvβ3 expressed within the tumor cell compartment to modulate the angiogenic output of a tumor. Here we provide evidence that αvβ3 expressed in melanoma cells may contribute to the suppression of IGFBP-4, an important negative regulator of IGF-1 signaling. Given the multiple context-dependent roles for αvβ3 in angiogenesis and tumor progression, our novel findings provide additional molecular insight into how αvβ3 may govern the angiogenic switch by a mechanism associated with a p38 MAPK and matrix metalloproteinases-dependent regulation of the endogenous angiogenesis inhibitor IGFBP-4.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of tumor-associated αvβ3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo

et al. 2014

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“…During malignant progression, the complex crosstalk between the IGF axis and integrin signaling contributes to enhanced cell survival, proliferation, migration and invasion (Beattie et al, 2010). Studies by Goel et al (2004Goel et al ( , 2005 have shown that IGF-IR signaling and its mitogenic and transforming activities in prostate cancer cells are regulated by b1 integrin and this involves direct interaction between the two molecules.…”

Section: Lung Metastasismentioning

confidence: 99%

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

et al. 2011

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The liver is a major site of metastasis for human malignancies, yet the factors that regulate tumor cell survival and growth in this organ remain elusive. Previously, we reported that M-27 IGFÀIR murine lung carcinoma cells with ectopic insulin-like growth factor-1 (IGF-I) receptor overexpression acquired a site-specific, liver-metastasizing potential. Gene expression profiling and subsequent RNA and protein analyses revealed that this was associated with major changes to the expression of extracellular matrix (ECM) protein-encoding genes including type III, IV and XVIII collagen genes, and these changes were also observed in the respective tumors in vivo. Because type IV collagen was the most prominently altered ECM protein in this model, we further analyzed its functional relevance to liver metastasis. M-27 cells stably overexpressing type IV collagen a1 and a2 chains were generated and their growth and metastatic properties investigated. We found that these cells acquired a site-selective growth advantage in the liver and this was associated with cell rescue from anoikis in a collagen IV/a2 integrin/FAK-dependent manner and increased responsiveness to IGF-I. Conversely, collagen IV or focal adhesion kinase (FAK) silencing by smallinterfering RNA in highly metastatic tumor cells enhanced anoikis and decreased liver metastases formation. Moreover, analysis of human surgical specimens revealed uniformly high collagen IV expression in 65/65 hepatic metastases analyzed, regardless of tissue of origin, whereas it was variable and generally low in 50/50 primary colorectal carcinoma specimens examined. The results suggest that collagen IV-conveyed signals are essential cues for liver metastasis in diverse tumor types and identify mediators of collagen IV signaling as potential therapeutic targets in the management of hepatic metastases.

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“…Key interacting protein families include the integrins at the cell surface (Beattie, et al 2010) and the nuclear hormone receptors within the nucleus (Yamada and Lee 2009). …”

Section: The Igfbpsmentioning

confidence: 99%

Involvement of the insulin-like growth factor binding proteins in the cancer cell response to DNA damage

Chua

Lin

Martin

et al. 2015

J. Cell Commun. Signal.

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The complex mechanisms that cells have evolved to meet the challenge of constant exposure to DNA‐damaging stimuli, also serve to protect cancer cells from the cytotoxic effects of chemo‐ and radiotherapy. IGFBPs appear to be involved, directly or indirectly, in some of these protective mechanisms. Activation of p53 is an early response to genotoxic stress, and all six human IGFBP genes have predicted p53 response elements in their promoter and/or intronic regions, at least some of which are functional. IGFBP3 has been extensively characterized as a p53‐inducible gene, but in some cases it is suppressed by mutant p53 forms. DNA double‐strand breaks (DSBs), induced by radiotherapy and some chemotherapies, potentially lead to apoptotic cell death, senescence, or repair and recovery. DSB damage can be repaired by homologous recombination or non‐homologous end‐joining (NHEJ), depending on the cell cycle stage, availability of key repair proteins, and other factors. The epidermal growth factor receptor (EGFR) has been implicated in the NHEJ pathway, and EGFR inhibition may inhibit repair, promoting apoptosis and thus improving sensitivity to chemotherapy or radiotherapy. Both IGFBP‐3 and IGFBP‐6 interact with components of the NHEJ pathway, and IGFBP‐3 can facilitate this process through direct interaction with both EGFR and the catalytic subunit of DNA‐PK. Cell fate after DNA damage may in part be regulated by the balance between the sphingolipids ceramide and sphingosine‐1‐phosphate, and IGFBPs can influence the production of both lipids. A better understanding of the involvement of IGFBPs in the DNA damage response in cancer cells may lead to improved methods of sensitizing cancers to DNA‐damaging therapies.

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Cross‐talk between the insulin‐like growth factor (IGF) axis and membrane integrins to regulate cell physiology

Cited by 31 publications

References 127 publications

Inhibition of tumor-associated αvβ3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo

Inhibition of tumor-associated αvβ3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

Involvement of the insulin-like growth factor binding proteins in the cancer cell response to DNA damage

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