Diversity of insulin and IGF signaling in breast cancer: Implications for therapy

Lero, Michael W.; Shaw, Leslie M.

doi:10.1016/j.mce.2021.111213

Cited by 47 publications

(42 citation statements)

References 139 publications

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“…New tumor markers with independent prognostic and predictive value are warranted since many patients are either over- or under-treated, signaling the need for more individualized treatment ( 2 ). Dysregulation of proteins in the insulin-like growth factor (IGF)/insulin signaling pathway has been described as a driver of breast cancer initiation and progression ( 3 ). However, there is still a lack of suitable biomarkers for treatments targeting this pathway ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…Dysregulation of proteins in the insulin-like growth factor (IGF)/insulin signaling pathway has been described as a driver of breast cancer initiation and progression ( 3 ). However, there is still a lack of suitable biomarkers for treatments targeting this pathway ( 3 ). An interesting candidate to be investigated as a novel biomarker is the insulin-like growth factor binding protein 7 (IGFBP7), also known as mac25/IGFBPrp1/angiomodulin (AGM)/prostacyclin-stimulating factor (PSF) or tumor adhesion factor (TAF) ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

et al. 2021

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The prognostic impact of insulin-like growth factor binding protein 7 (IGFBP7) in breast cancer is unclear. Host factors, including lifestyle, anthropometry, and metabolic profile, might influence tumor-specific IGFBP7. This study aimed to investigate whether IGFBP7 levels and mRNA expression are associated with the patient and tumor characteristics and prognosis in breast cancer. Patients with primary breast cancer in Lund, Sweden, were included preoperatively in the study between 2002 and 2012 (n = 1018). Tumor-specific IGFBP7 protein levels were evaluated with immunohistochemistry using tissue microarrays in tumors from 878 patients. IGFBP7 mRNA expression and its corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and analyzed for 809 patients. Tumor-specific IGFBP7 protein levels were categorized based on Histo 300 scores into IGFBP7low (6.2%), IGFBP7intermediate (75.7%), and IGFBP7high (18.1%). Both low IGFBP7 protein levels and mRNA expression were associated with less aggressive tumor characteristics. Overall, IGFBP7low conferred low recurrence risk. The prognostic impact of IGFBP7high varied according to any alcohol consumption and tamoxifen treatment. IGFBP7high was associated with low recurrence risk in alcohol consumers but high recurrence risk in alcohol abstainers (Pinteraction= 0.039). Moreover, the combination of IGFBP7high and estrogen receptor-positive tumors was associated with low recurrence risk only in tamoxifen-treated patients (Pinteraction= 0.029). To conclude, IGFBP7low might be a good, independent prognosticator in breast cancer. The prognostic impact of IGFBP7high depends on host factors and treatment. IGFBP7 merits further investigation to confirm whether it could be a suitable biomarker for treatment selection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

et al. 2021

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“…Центральным событием является активация фосфатидилинозитол-3-киназой протеинкиназы В (AKT), через которую осуществляется регуляция метаболических эффектов инсулина и IGFs-регуляция поглощения глюкозы клетками для контроля ее гомеостаза, индукция гликолиза, негативная регуляция синтеза гликогена, липогенеза, глюконеогенеза, регуляция активности рапамицинового комплекса млекопитающих 1 (mTORC1), который опосредует регуляцию липогенеза и липолиза [37,41]. Через путь PI3K-AKT и mTORC1 реализуется и часть митогенных эффектов инсулина -дезактивация и деградация фактора транскрипции FOXO, отменяющая остановку клеточного цикла и активирующая подавление апоптоза клеток, индуцируется накопление в ядре клетки циклина D1, регулирующего фазовый переход клетки G1/S [37,41]. В основном же митогенные эффекты (рост, пролиферация, дифференцировка, выживание клеток) опосредует активация сигнального пути RAS/MAPK/ERK.…”

Section: структурные элементы сигнальной системы инсулина и оси Igf/igfbpunclassified

Diabetes mellitus and cancer: a system of insulin-like growth factors

Frantsiyants¹,

Surikova²,

Kaplieva³

et al. 2021

Probl Endokrinol (Mosk)

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Diabetes mellitus and malignant tumors are among the most common and complex diseases. Epidemiological studies have shown a strong relationship between these pathologies. The causality of this relationship has not yet been unambiguously established, but a number of probable biological mechanisms have been proposed to explain it through the effects of hyperglycemia, hyperinsulinemia on the process of oncogenesis. An important role in this is played by the axis of insulin-like growth factors, their receptors and binding proteins (IGF / IGFR / IGFBP). The review provides data on the structural elements of the insulin / IGF / IGFR / IGFBP signaling axis and their internal relationships in diabetes mellitus and in the development of malignant tumors. Significant changes in the axis that occur during the formation of the diabetic environment prepare the background, which, under certain conditions, can lead to the stimulation or inhibition of tumor development. The considered signaling system, playing a significant role in the physiology of normal cells, often functions as a decisive factor in the survival of tumor cells, providing fine context-dependent regulation of many cellular processes associated with oncogenesis. However, despite many years of in-depth studies of the pathogenesis of diabetes mellitus and malignant tumors, the molecular mechanisms of the relationship between these pathologies are still largely unclear, and the internal heterogeneity of pathologies complicates research and interpretation of the results, leaving many questions.

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“…Receptor tyrosine kinases (RTKs) have been implicated in promoting metastatic properties in tumor cells. RTK domain mutations are not a prominent feature in most cancers; instead, RTK expression level is the general driver of tumorigenesis and metastasis (1)(2)(3)(4). A well-known RTK that has a prominent role in a subclass of breast cancers and has been the focus for successful cancer therapeutics is HER2.…”

Section: Mainmentioning

confidence: 99%

Breast tumor Insulin-like growth factor receptor regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics

Obr

Chang

Ciliento

et al. 2021

Preprint

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The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer, low levels of IGF-1R expression are associated with worse overall patient survival. To determine how reduced IGF-1R impacts tumor phenotype, we used weighted correlation gene network analysis (WCGNA) of METABRIC patient data and identified gene modules specific to cell cycle, adhesion, and immune cell signaling inversely correlated with IGF-1R expression in human breast cancers. Integration of human patient data with data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like tumors with reduced signaling or expression of the IGF-1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.

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Diversity of insulin and IGF signaling in breast cancer: Implications for therapy

Cited by 47 publications

References 139 publications

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

Diabetes mellitus and cancer: a system of insulin-like growth factors

Breast tumor Insulin-like growth factor receptor regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics

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