Role of IGF1R in Breast Cancer Subtypes, Stemness, and Lineage Differentiation

Farabaugh, Susan M.; Boone, David N.; Lee, Adrian V.

doi:10.3389/fendo.2015.00059

Cited by 158 publications

(135 citation statements)

References 171 publications

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“…However, compensation and activating feedback mechanisms collectively depress the efficacy of anti-IGF1R/InsR therapies (11). Only after discerning the dual IGF1R/InsR system dynamics and novel components, will we be able to start to direct patients with suitable tumor subclasses toward more efficient personalized clinical interventions.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways

Erdem

Nagle

Casà

et al. 2016

Molecular & Cellular Proteomics

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Insulin and insulin-like growth factor I (IGF1) influence cancer risk and progression through poorly understood mechanisms. To better understand the roles of insulin and IGF1 signaling in breast cancer, we combined proteomic screening with computational network inference to uncover differences in IGF1 and insulin induced signaling. Using reverse phase protein array, we measured the levels of 134 proteins in 21 breast cancer cell lines stimulated with IGF1 or insulin for up to 48 h. We then constructed directed protein expression networks using three separate methods: (i) lasso regression, (ii) conventional matrix inversion, and (iii) entropy maximization. These networks, named here as the time translation models, were analyzed and the inferred interactions were ranked by differential magnitude to identify pathway differences. Insulin (Ins)1 and type I insulin-like growth factor (IGF1) receptors (InsR and IGF1R, respectively) are receptor tyrosine kinases that are expressed in almost all types of cells. Signaling through InsR and IGF1R initiates a phosphorylation cascade that drives cell growth and proliferation (1-8). Overexpression of these receptors is correlated with higher breast cancer risk (9 -15) and has been shown to influence tumorigenesis, metastasis, and resistance to existing forms of cancer therapy (10,16,17). IGF receptor blockade can slow tumor growth and metastasis, but the receptor has proven to be difficult to target specifically (18 -20). A confounding factor in developing therapies targeting these receptors is their high sequence (ϳ60%) and structural homology. IGF1R and InsR are able to form functional hybrids, and each can partially compensate for the loss or suppression of the other (1-4, 21-24). Moreover, it has been shown that IGF1R signaling is one mechanism of resistance to conventional hormonal therapy (19,(25)(26)(27)(28)(29). Understanding the relationships between IGF1R and InsR signaling cascades and their combinatorial role in cancer is crucial to developing better diagnostics and personalized treatments for cancer.

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Section: Discussionmentioning

confidence: 99%

Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways

Erdem

Nagle

Casà

et al. 2016

Molecular & Cellular Proteomics

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“…The authors further indicated that IGFIR mRNA extend to be more highly expressed in Luminal A and B subtypes compared with the basal-like and HER2-positive subtypes (173). Many IGFIR inhibitors (mAbs and TKIs) and IGF1/IGF2 neutralizing mABs have been developed and evaluated in clinical trials with some success in early trials but have failed to show benefits in larger phase III trials (174).…”

Section: Other Rtksmentioning

confidence: 96%

“…Analysis of TCGA database indicated that IGFIR is amplified, overexpressed, or somatically mutated in 9% of breast tumors (173). The authors further indicated that IGFIR mRNA extend to be more highly expressed in Luminal A and B subtypes compared with the basal-like and HER2-positive subtypes (173).…”

Section: Other Rtksmentioning

confidence: 99%

The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer

Hsu

Hung

2016

Cancer Metastasis Rev

291

185

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Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the United States will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer. However, not all breast cancers are the same as evidenced by the multiple subtypes of the disease, with some more aggressive than others, showing differential treatment response to different types of drugs. Moreover, in addition to canonical signaling from the cell surface, many RTKs can be trafficked to various subcellular compartments, such as the multivesicular body and nucleus, where they carry out critical cellular functions, such as cell proliferation, DNA replication and repair, and therapeutic resistance. In this review, we provide a brief summary on the role of a selected number of RTKs in breast cancer and describe some mechanisms of resistance.

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“…The results showed overexpression of IGF-1R in EpCAM(+) exosomes of NSCLC patients relative to controls, while no correlation between p-IGF-1R and disease state or IGF-1R levels was found. Given the significant interest in these proteins for cancer diagnosis and treatment, 116–118 the pioneering exosome-based analysis performed could be important for establishing IGF-1R and p-IGF-1R as exosomal biomarkers. Although μNMR and nPLEX also performed on-chip detection of intravesicular proteins, such as HSP70, HSP90, and IDH1 R132H, some samples were from cell cultures and off-chip exosome isolation and/or lysis was required.…”

Section: Integrated Microfluidic Platforms For Exosome Analysismentioning

confidence: 99%

Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

2017

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Exosomes, the smallest sized extracellular vesicles (30 ~ 150 nm) packaged with lipids, proteins, functional messenger RNAs and microRNAs, and double-stranded DNA from their cells of origin, have emerged as key players in intercellular communication. Their presence in bodily fluids, where they protect their cargo from degradation, makes them attractive candidates for clinical application as innovative diagnostic and therapeutic tools. But routine isolation and analysis of high purity exosomes in clinical settings is challenging, with conventional methods facing a number of drawbacks including low yield and/or purity, long processing times, high cost, and difficulties in standardization. Here we review a promising solution, microfluidic-based technologies that have incorporated a host of separation and sensing capabilities for exosome isolation, detection, and analysis, with emphasis on point of care and clinical applications. These new capabilities promise to advance fundamental research while paving the way toward routine exosome-based liquid biopsy for personalized medicine.

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Role of IGF1R in Breast Cancer Subtypes, Stemness, and Lineage Differentiation

Cited by 158 publications

References 171 publications

Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways

Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways

The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer

Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

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