Modulation of JAK-STAT Signaling by LNK: A Forgotten Oncogenic Pathway in Hormone Receptor-Positive Breast Cancer

López-Mejía, José A.; Mantilla-Ollarves, Jessica C.; Rocha-Zavaleta, Leticia

doi:10.3390/ijms241914777

Cited by 11 publications

(4 citation statements)

References 149 publications

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“…This is consistent with the expectation that there are many biological pathways to BC aside from ER agonism and E2/P4 steroidogenesis, including genotoxicity, 5 other types of endocrine signaling, 16 , 51 , 104 and multiple other KCs. 16 , 105 , 106 On the other hand, genotoxicity was highly sensitive for detecting MCs but poorly specific given that many non-MCs were also genotoxic.…”

Section: Resultsmentioning

confidence: 99%

Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly Available in Vivo , in Vitro , and in Silico Data

Kay,

Brody,

Schwarzman

et al. 2024

Environ Health Perspect

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Background: Chemicals that induce mammary tumors in rodents or activate estrogen or progesterone signaling are likely to increase breast cancer (BC) risk. Identifying chemicals with these activities can prompt steps to protect human health. Objectives: We compiled data on rodent tumors, endocrine activity, and genotoxicity to assess the key characteristics (KCs) of rodent mammary carcinogens (MCs), and to identify other chemicals that exhibit these effects and may therefore increase BC risk. Methods: Using authoritative databases, including International Agency for Research on Cancer (IARC) Monographs and the US Environmental Protection’s (EPA) ToxCast, we selected chemicals that induce mammary tumors in rodents, stimulate estradiol or progesterone synthesis, or activate the estrogen receptor (ER) in vitro . We classified these chemicals by their genotoxicity and strength of endocrine activity and calculated the overrepresentation (enrichment) of these KCs among MCs. Finally, we evaluated whether these KCs predict whether a chemical is likely to induce mammary tumors. Results: We identified 279 MCs and an additional 642 chemicals that stimulate estrogen or progesterone signaling. MCs were significantly enriched for steroidogenicity, ER agonism, and genotoxicity, supporting the use of these KCs to predict whether a chemical is likely to induce rodent mammary tumors and, by inference, increase BC risk. More MCs were steroidogens than ER agonists, and many increased both estradiol and progesterone. Enrichment among MCs was greater for strong endocrine activity vs. weak or inactive, with a significant trend. Discussion: We identified hundreds of compounds that have biological activities that could increase BC risk and demonstrated that these activities are enriched among MCs. We argue that many of these should not be considered low hazard without investigating their ability to affect the breast, and chemicals with the strongest evidence can be targeted for exposure reduction. We describe ways to strengthen hazard identification, including improved assessments for mammary effects, developing assays for more KCs, and more comprehensive chemical testing. https://doi.org/10.1289/EHP13233

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Section: Resultsmentioning

confidence: 99%

Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly Available in Vivo , in Vitro , and in Silico Data

Kay,

Brody,

Schwarzman

et al. 2024

Environ Health Perspect

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“…Luminal B subtype GO exclusive categories include processes related to T-cell response through molecules like the CD4 co-receptor and signal transduction components like FOS, JUN, and JAK3 ( 76 , 77 ). Other processes associated with immune system signaling or hematopoiesis are represented by HSPA family members HSPA1A and HSPA1B.…”

Section: Resultsmentioning

confidence: 99%

Coordinated inflammation and immune response transcriptional regulation in breast cancer molecular subtypes

Velazquez-Caldelas,

Zamora-Fuentes,

Hernandez-Lemus

2024

Front. Immunol.

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Breast cancer, characterized by its complexity and diversity, presents significant challenges in understanding its underlying biology. In this study, we employed gene co-expression network analysis to investigate the gene composition and functional patterns in breast cancer subtypes and normal breast tissue. Our objective was to elucidate the detailed immunological features distinguishing these tumors at the transcriptional level and to explore their implications for diagnosis and treatment. The analysis identified nine distinct gene module clusters, each representing unique transcriptional signatures within breast cancer subtypes and normal tissue. Interestingly, while some clusters exhibited high similarity in gene composition between normal tissue and certain subtypes, others showed lower similarity and shared traits. These clusters provided insights into the immune responses within breast cancer subtypes, revealing diverse immunological functions, including innate and adaptive immune responses. Our findings contribute to a deeper understanding of the molecular mechanisms underlying breast cancer subtypes and highlight their unique characteristics. The immunological signatures identified in this study hold potential implications for diagnostic and therapeutic strategies. Additionally, the network-based approach introduced herein presents a valuable framework for understanding the complexities of other diseases and elucidating their underlying biology.

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“…Numerous reports suggest that the acquisition of mutations that alter the function of STAT proteins underlies tumor cell genesis ( 25 – 28 ). STAT proteins do not accomplish tasks independently and function alongside cytokines, inducible factor expression or phosphorylation modifications ( 29 ). When JAK/STAT ligand and receptor binding is activated, JAK binds non-covalently to the receptor structure, after which the kinase activity of JAK is activated and phosphorylates the tyrosine residues in the receptor region.…”

Section: Signal Regulation In Breast Cancermentioning

confidence: 99%

Role of microRNAs in triple‑negative breast cancer and new therapeutic concepts (Review)

Yang,

2024

Oncol Lett

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Breast cancer has surpassed lung cancer as the most prevalent malignancy affecting women worldwide. Triple-negative breast cancer (TNBC) is the type of breast cancer with the worst prognosis. As a heterogeneous disease, TNBC has a pathogenesis that involves multiple oncogenic pathways, including involvement of gene mutations and alterations in signaling pathways. MicroRNAs (miRNAs) are small endogenous, single-stranded non-coding RNAs that bind to the 3′ untranslated region of target cell mRNAs to negatively regulate the gene expression of these specific mRNAs. Therefore, miRNAs are involved in cell growth, development, division and differentiation stages. miRNAs are also involved in gene targeting in tumorigenesis, tumor growth and the regulation of metastasis, including in breast cancer. Meanwhile, miRNAs also regulate components of signaling pathways. In this review, the role of miRNAs in the TNBC signaling pathway discovered in recent years is described in detail. The new concept of bi-targeted therapy for breast cancer using miRNA and artificial intelligence is also discussed.

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Modulation of JAK-STAT Signaling by LNK: A Forgotten Oncogenic Pathway in Hormone Receptor-Positive Breast Cancer

Cited by 11 publications

References 149 publications

Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly Available in Vivo , in Vitro , and in Silico Data

Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly Available in Vivo , in Vitro , and in Silico Data

Coordinated inflammation and immune response transcriptional regulation in breast cancer molecular subtypes

Role of microRNAs in triple‑negative breast cancer and new therapeutic concepts (Review)

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