Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

Yuan, Jingsheng; Yin, Zhe; Tao, Kaixiong; Wang, Guobing; Gao, Jinbo

doi:10.3892/ol.2017.7276

Cited by 75 publications

(82 citation statements)

References 98 publications

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“…In these cancers paracrine/autocrine GH induces oncogenic signaling for classical oncogenic processes like proliferation, migration, invasion, angiogenesis [87] , metastasis [65] , and avoiding apoptosis [88] . IGF1, one of the principal effectors of GH action, is also [89] important in progression of specific transformed cells and in driving therapy resistance in cancer [90] . While several reviews have described the effects of GH action in cancer prognosis and progression, the unique role and molecular details of GH-GHR action in promoting the resistance of tumors to therapy has not been reviewed.…”

Section: Gh-ghr In Cancermentioning

confidence: 99%

The effects of growth hormone on therapy resistance in cancer

Basu¹,

Kopchick²

2019

CDR

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Pituitary derived and peripherally produced growth hormone (GH) is a crucial mediator of longitudinal growth, organ development, metabolic regulation with tissue specific, sex specific, and age-dependent effects. GH and its cognate receptor (GHR) are expressed in several forms of cancer and have been validated as an anti-cancer target through a large body of in vitro, in vivo and epidemiological analyses. However, the underlying molecular mechanisms of GH action in cancer prognosis and therapeutic response had been sparse until recently. This review assimilates the critical details of GH-GHR mediated therapy resistance across different cancer types, distilling the therapeutic implications based on our current understanding of these effects.

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Section: Gh-ghr In Cancermentioning

confidence: 99%

The effects of growth hormone on therapy resistance in cancer

Basu¹,

Kopchick²

2019

CDR

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“…Insulin-like growth factor signaling has been implicated in the growth and survival of both normal and malignant cells. IGF1R expression and activity increase in several tumor types, including breast cancer [41], resulting in enhanced proliferation rate, metastatic capacity, and resistance to chemotherapy [42]. Therefore, targeting of the IGF axis has been in the focus of therapeutic approach developments in numerous malignant diseases [43].…”

Section: Discussionmentioning

confidence: 99%

Pericyte‐secreted IGF2 promotes breast cancer brain metastasis formation

et al. 2020

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Brain metastases are life‐threatening complications of triple‐negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo and in vitro techniques and human samples, here we show that pericytes play crucial role in the development of metastatic brain tumors by directly influencing key steps of the development of the disease. Brain pericytes had a prompt chemoattractant effect on breast cancer cells and established direct contacts with them. By secreting high amounts of extracellular matrix proteins, pericytes enhanced adhesion of both melanoma and triple‐negative cancer cells, which might be particularly important in the exclusive perivascular growth of these tumor cells. In addition, pericytes secreted insulin‐like growth factor 2 (IGF2), which had a very significant pro‐proliferative effect on mammary carcinoma, but not on melanoma cells. By inhibiting IGF2 signaling using silencing or picropodophyllin (PPP), we could block the proliferation‐increasing effect of pericytes on breast cancer cells. Administration of PPP (a blood–brain barrier‐permeable substance) significantly decreased the size of brain tumors in mice inoculated with triple‐negative breast cancer cells. Taken together, our results indicate that brain pericytes have significant pro‐metastatic features, especially in breast cancer. Our study underlines the importance of targeting pericytes and the IGF axis as potential strategies in brain metastatic diseases.

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“…AKT abnormal overexpression or activation has been reported in many human solid tumors and hematological malignancies, being associated with increased cancer cell proliferation and survival and becoming an important cancer therapeutic target (136,137). Receptor tyrosine kinases, such as IGF-1R, EGFR, human epidermal growth factor receptor 2 (HER2/ErbB2) and platelet-derived growth factor receptor (PDGFR), are activated in many cancers, and they trigger downstream signal cascades, including RAS/RAF/MAPK and PI3K/AKT signaling pathways (138)(139)(140)(141).…”

Section: Insulin-like Growth Factor (Igf) Systemmentioning

confidence: 99%

Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

Mollinedo

Gajate

2020

Journal of Lipid Research

187

206

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Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

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Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

Cited by 75 publications

References 98 publications

The effects of growth hormone on therapy resistance in cancer

The effects of growth hormone on therapy resistance in cancer

Pericyte‐secreted IGF2 promotes breast cancer brain metastasis formation

Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

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