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The regulation of insulin receptor/insulin-like growth factor 1 receptor ratio, an important factor for breast cancer prognosis, by TRIP-Br1.

ABSTRACT: Much higher risk of cancer has been found in diabetes patients. Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) have been extensively studied in both breast cancer and diabetes therapies. Interestingly, a recent study proposed that IR/IGF1R ratio is an important factor for breast cancer prognosis. Women with higher IR/IGF1R ratio showed poor breast cancer prognosis as well as hyperinsulinemia. Here, we propose a novel mechanism that oncogenic protein TRIP-Br1 renders breast cancer cells and insulin deficient mice to have higher IR/IGF1R ratio by positively and negatively regulating IR and IGF1R expression at the protein level, respectively. TRIP-Br1 repressed IR degradation by suppressing its ubiquitination. Meanwhile, TRIP-Br1 directly interacts with both IGF1R and NEDD4-1 E3 ubiquitin ligase, in which TRIP-Br1/NEDD4-1 degrades IGF1R via ubiquitin/proteasome system. TRIP-Br1-mediated higher IR/IGF1R ratio enhanced the proliferation and survival of breast cancer cells. In conclusion, current study may provide an important information in the regulatory mechanism of how breast cancer cells have acquired higher IR/IGF1R ratio.

SUBMITTER: Nguyen TNQ

PROVIDER: S-EPMC9204904 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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The regulation of insulin receptor/insulin-like growth factor 1 receptor ratio, an important factor for breast cancer prognosis, by TRIP-Br1.

Nguyen Thi Ngoc Quynh TNQ Jung Samil S Nguyen Hai Anh HA Lee BeomSuk B Vu Son Hai SH Myagmarjav Davaajargal D Eum Hye Hyeon HH Lee Hae-Ock HO Jo Taeyeon T Choi Yeongseon Y Lee Myeong-Sok MS

Journal of hematology & oncology 20220616 1

Much higher risk of cancer has been found in diabetes patients. Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) have been extensively studied in both breast cancer and diabetes therapies. Interestingly, a recent study proposed that IR/IGF1R ratio is an important factor for breast cancer prognosis. Women with higher IR/IGF1R ratio showed poor breast cancer prognosis as well as hyperinsulinemia. Here, we propose a novel mechanism that oncogenic protein TRIP-Br1 renders brea ...[more]

PMID: 35710446

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Project description:PurposeInsulin stimulates eye growth in chicks and this effect is greatly enhanced if the retinal image is degraded by the defocus of either sign. However, it is unclear whether the insulin receptor (IR) is expressed at all in the chicken retina in animals 1-2 weeks post-hatching. We have investigated IR expression and whether IR transcript abundance varies in the fundal layers. To elucidate the possible role of insulin and insulin-like growth factor (IGF)-1 signaling in eye growth regulation, mRNA (mRNA) levels were measured for insulin, IGF-1, IR, and IGF-1 receptor (IGF-1R) during imposed negative or positive defocus.MethodsChicks were treated binocularly with positive or negative spectacle lenses for 4 or 24 h, or they remained untreated (n=6, for each treatment group). Northern blot analyses were performed to screen for transcription variants in the different fundal layers of untreated animals. Real-time PCR was used to quantify IR, IGF-1R, IGF-1, and insulin mRNA levels in the different fundal layers of the chick eye in the three treatment groups.ResultsIR mRNA was found in all the studied tissues, although there is evidence of tissue-specific transcript variations. Three major transcripts were detected for IR. The brain, retina, and choroid showed the longest transcript (4.3 kb), which was not present in the liver. Nevertheless, the liver and brain showed a second transcript (2.6 kb) not present in the retina and choroid. A short transcript (1.3 kb) was the predominant form in the liver and choroid, and it seems to be present in the retinal pigment epithelium (RPE) and sclera as well. In the retina, no significant gene expression changes were found when defocus was imposed. Interestingly, in the RPE, both IR and IGF-1R were already downregulated after short periods (4 h) of positive lens wear. In contrast, IR and IGF-1R were upregulated in the choroid and fibrous sclera during treatment with negative, but not positive, lenses.ConclusionsDifferences observed in the IR transcript length in different tissues suggest possibly different functions. The differential regulation of IR and IGF-1R in the RPE, choroid, and fibrous sclera is consistent with their involvement in a signaling cascade for emmetropization.

Dataset Information

The regulation of insulin receptor/insulin-like growth factor 1 receptor ratio, an important factor for breast cancer prognosis, by TRIP-Br1.

Publications

The regulation of insulin receptor/insulin-like growth factor 1 receptor ratio, an important factor for breast cancer prognosis, by TRIP-Br1.

Similar Datasets

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