ArticleHormones & cancer2018
Insulin Receptor Substrate Suppression by the Tyrphostin NT157 Inhibits Responses to Insulin-Like Growth Factor-I and Insulin in Breast Cancer Cells.
Article in Hormones & cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer.The Journal of biological chemistry · 2026Article
- Unraveling Diabetes Mellitus-Driven Tumorigenesis: From Pathophysiological Mechanisms, Therapeutic Drugs to Tailor-Made Nanosystems.International journal of nanomedicine · 2026Review
- NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma.Hematology, transfusion and cell therapy · 2024Article
- Microproteomic-Based Analysis of the Goat Milk Protein Synthesis Network and Casein Production Evaluation.Foods (Basel, Switzerland) · 2024Article
- ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.NPJ breast cancer · 2023Article
- Suppression of Insulin Receptor Substrate 1 Inhibits Breast Cancer Growth In Vitro and in Female Athymic Mice.Endocrinology · 2023Article
- NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells.Scientific reports · 2022Article
- Embryonic Programs in Cancer and Metastasis-Insights From the Mammary Gland.Frontiers in cell and developmental biology · 2022Review
- MiR-98-5p/IGF2 Axis Influence Herceptin Sensitivity through IGF1R/HER2 Heterodimer Formation and AKT/mTOR Signal Pathway in HER2 Positive Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- PELP1/SRC-3-dependent regulation of metabolic PFKFB kinases drives therapy resistant EROncogene · 2021Article
- NT157, an IGF1R-IRS1/2 inhibitor, exhibits antineoplastic effects in pre-clinical models of chronic myeloid leukemia.Investigational new drugs · 2021Article
- Disrupting Insulin and IGF Receptor Function in Cancer.International journal of molecular sciences · 2021Review
- Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer.British journal of cancer · 2021Article
- Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.Journal of hematology & oncology · 2020Review
- The Continuing Evolution of Insulin-like Growth Factor Signaling.F1000Research · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin and insulin-like growth factor (IGF) signaling systems regulate breast cancer growth, progression, and metastasis. The insulin receptor substrates 1 and 2 (IRS1/2) transduce signaling from the type I IGF receptor (IGF-IR) and insulin receptor (InR) to mediate the biological effects of receptor activation. In breast cancer, IRS-1 plays a critical role in cancer cell proliferation while IRS-2 is associated with motility and metastasis. NT157, a small-molecule tyrphostin, downregulates IRS proteins in several model systems. In breast cancer cells, NT157 treatment suppressed IRS protein expression in a dose-dependent manner. Exposure to NT157 inhibited the activation of downstream signaling mediated by the IRS proteins. NT157 induced a MAPK-dependent serine phosphorylation of IRS proteins which resulted in disassociation between IRS proteins and their receptors resulting in IRS degradation. In estrogen receptor-α-positive (ERα+) breast cancer cells (MCF-7 and T47D), NT157 also resulted in cytoplasmic ERα downregulation likely because of disruption of an IRS-1-IGF-IR/InR/ERα complex. NT157 decreased S phase fraction, monolayer, and anchorage-independent growth after IGF/insulin treatment in ERα+ breast cancer cells. NT157 downregulation of IRS protein expression also sensitized ERα+ breast cancer cells to rapamycin. Moreover, NT157 inhibited the growth of tamoxifen-resistant ERα+ breast cancer cells. Given that both IGF-IR and InR play a role in cancer biology, targeting of IRS adaptor proteins may be a more effective strategy to inhibit the function of these receptors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.