The impact of the IGF-1 system of cancer cells on radiation response – An in vitro study

Venkatachalam, Senthiladipan; Mettler, Esther; Fottner, Christian; Miederer, Matthias; Kaina, Bernd; Weber, Matthias M.

doi:10.1016/j.ctro.2017.09.006

Cited by 18 publications

(12 citation statements)

References 50 publications

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“…Very few studies have been conducted on the role of IGF‐1R in resistance to radiation therapy. In multiple studies, it has been shown that suppression of IGF‐1R ROS‐mediated overactivation leads to the decreased radioresistance of different cancers both in vitro and in vivo (Denduluri et al, ; Moreno‐Acosta et al, ; Panganiban & Day, ; Venkatachalam et al, ; Yavari et al, ). In this regard, findings from Afshar () study have shown that inhibition of IGF‐1R by ectopic increase of miR‐185 suppressed radiation‐induced IGF‐1R phosphorylation/overactivation and introduced apoptosis and then radiosensitivity in CRC cell line.…”

Section: Discussionmentioning

confidence: 99%

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Samadi

Afshar

Amini

et al. 2018

Journal Cellular Physiology

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Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let‐7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let‐7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin‐like growth factor 1 receptor (IGF‐1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF‐1R is a direct target of the let‐7e member. Consistent with this, we identified that increased levels of let‐7e in CRC cells reduced IGF‐1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let‐7e by targeting the IGF‐1R signaling pathway might serve as therapeutics in anticancer therapy.

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Section: Discussionmentioning

confidence: 99%

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Samadi

Afshar

Amini

et al. 2018

Journal Cellular Physiology

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“…IGF-1 exerts pleiotropic effects in autocrine, paracrine, and endocrine fashions [ 2 ] by binding to its cognate IGF-1 receptors on target cells. IGF-1 signal transduction activates several downstream proteins involved in cell survival, proliferation, propagation [ 3 ], and confers radioresistance properties to tumor cells [ 4 ]. Other researchers have reported an association between aging and an increase in radiation sensitivity [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Dysregulated Cardiac IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity

Aghdam

Kenchegowda

Sharma

et al. 2020

IJMS

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Acute exposure to ionizing radiation leads to Hematopoietic Acute Radiation Syndrome (H-ARS). To understand the inter-strain cellular and molecular mechanisms of radiation sensitivity, adult males of two strains of minipig, one with higher radiosensitivity, the Gottingen minipig (GMP), and another strain with comparatively lower radiosensitivity, the Sinclair minipig (SMP), were exposed to total body irradiation (TBI). Since Insulin-like Growth Factor-1 (IGF-1) signaling is associated with radiation sensitivity and regulation of cardiovascular homeostasis, we investigated the link between dysregulation of cardiac IGF-1 signaling and radiosensitivity. The adult male GMP; n = 48, and SMP; n = 24, were irradiated using gamma photons at 1.7–2.3 Gy doses. The animals that survived to day 45 after irradiation were euthanized and termed the survivors. Those animals that were euthanized prior to day 45 post-irradiation due to severe illness or health deterioration were termed the decedents. Cardiac tissue analysis of unirradiated and irradiated animals showed that inter-strain radiosensitivity and survival outcomes in H-ARS are associated with activation status of the cardiac IGF-1 signaling and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidant gene expression. Our data link H-ARS with dysregulation of cardiac IGF-1 signaling, and highlight the role of oxidative stress and cardiac antioxidant response in radiation sensitivity.

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“…Given the established role of IGF-1 signaling in radiation sensitivity [ 31 ], in the current report we explored the possibility of whether the link between tissue IGF-1 signaling and radiation sensitivity could be extrapolated to other animal models and if the quality and maintenance of normal IGF-1 signaling in tissues other than heart would show similarities to heart tissue. At a molecular level, we also explored the link between cardiac mitochondrial energy metabolism, cardiac antioxidant gene response mediated by Nrf2 transcription factor and their association with the radiation sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality

Aghdam¹,

Kenchegowda²,

Holmes-Hampton³

et al. 2021

IJMS

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Following exposure to high doses of ionizing radiation, diverse strains of vertebrate species will manifest varying levels of radiation sensitivity. To understand the inter-strain cellular and molecular mechanisms of radiation sensitivity, two mouse strains with varying radiosensitivity (C3H/HeN, and CD2F1), were exposed to total body irradiation (TBI). Since Insulin-like Growth Factor-1 (IGF-1) signaling pathway is associated with radiosensitivity, we investigated the link between systemic or tissue-specific IGF-1 signaling and radiosensitivity. Adult male C3H/HeN and CD2F1 mice were irradiated using gamma photons at Lethal Dose-70/30 (LD70/30), 7.8 and 9.35 Gy doses, respectively. Those mice that survived up to 30 days post-irradiation, were termed the survivors. Mice that were euthanized prior to 30 days post-irradiation due to deteriorated health were termed decedents. The analysis of non-irradiated and irradiated survivor and decedent mice showed that inter-strain radiosensitivity and post-irradiation survival outcomes are associated with activation status of tissue and systemic IGF-1 signaling, nuclear factor erythroid 2–related factor 2 (Nrf2) activation, and the gene expression profile of cardiac mitochondrial energy metabolism pathways. Our findings link radiosensitivity with dysregulation of IGF-1 signaling, and highlight the role of antioxidant gene response and mitochondrial function in radiation sensitivity.

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The impact of the IGF-1 system of cancer cells on radiation response – An in vitro study

Cited by 18 publications

References 50 publications

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Dysregulated Cardiac IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity

Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality

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