Non-Genomic Actions of Estrogens on the DNA Repair Pathways Are Associated With Chemotherapy Resistance in Breast Cancer

Jiménez-Salazar, Javier Esteban; Damián-Ferrara, Rebeca; Arteaga, Marcela; Batina, Nikola; Damián-Matsumura, Pablo

doi:10.3389/fonc.2021.631007

Cited by 9 publications

(7 citation statements)

References 85 publications

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“…Estrogen signaling pathway is one of the most important pathways involved in steroid hormones and reproductive regulation in mammals ( Saito and Cui, 2018 ), and estrogens are also associated with tumor development, particularly breast and ovary cancers ( Ferreira et al, 2009 ). Studies also demonstrated that estrogen is also related to the DNA repair pathways and DNA integrity ( Jiménez-Salazar et al, 2021 ; Pescatori et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Radiation Can Cause Epigenetic Alterations Associated With Impairments in Both Male and Female Reproductive Cells

Leung

Yang

et al. 2021

Front. Genet.

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Humans are regularly and continuously exposed to ionizing radiation from both natural and artificial sources. Cumulating evidence shows adverse effects of ionizing radiation on both male and female reproductive systems, including reduction of testis weight and sperm count and reduction of female germ cells and premature ovarian failure. While most of the observed effects were caused by DNA damage and disturbance of DNA repairment, ionizing radiation may also alter DNA methylation, histone, and chromatin modification, leading to epigenetic changes and transgenerational effects. However, the molecular mechanisms underlying the epigenetic changes and transgenerational reproductive impairment induced by low-dose radiation remain largely unknown. In this study, two different types of human ovarian cells and two different types of testicular cells were exposed to low dose of ionizing radiation, followed by bioinformatics analysis (including gene ontology functional analysis and Ingenuity Pathway Analysis), to unravel and compare epigenetic effects and pathway changes in male and female reproductive cells induced by ionizing radiation. Our findings showed that the radiation could alter the expression of gene cluster related to DNA damage responses through the control of MYC. Furthermore, ionizing radiation could lead to gender-specific reproductive impairment through deregulation of different gene networks. More importantly, the observed epigenetic modifications induced by ionizing radiation are mediated through the alteration of chromatin remodeling and telomere function. This study, for the first time, demonstrated that ionizing radiation may alter the epigenome of germ cells, leading to transgenerational reproductive impairments, and correspondingly call for research in this new emerging area which remains almost unknown.

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Section: Discussionmentioning

confidence: 99%

Low-Dose Radiation Can Cause Epigenetic Alterations Associated With Impairments in Both Male and Female Reproductive Cells

Leung

Yang

et al. 2021

Front. Genet.

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“…Given the key role of this receptor in the growth and survival of hormone-dependent cancer cells, ERα constitutes an important diagnostic and therapeutic target. ERα thus regulates the transcription of many genes involved in cell proliferation through genomic and nongenomic actions [ 151 , 152 , 153 , 154 , 155 ]. While the classical genomic effects are better established, the impact of the non-genomic plasma membrane receptor pathway as well as the rapid stimulation of intracellular signaling cascades are still under active investigation.…”

Section: Discussionmentioning

confidence: 99%

A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer

Clusan

Ferrière

Flouriot

et al. 2023

IJMS

111

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Breast cancer is the most common cancer and the deadliest among women worldwide. Estrogen signaling is closely associated with hormone-dependent breast cancer (estrogen and progesterone receptor positive), which accounts for two-thirds of tumors. Hormone therapy using antiestrogens is the gold standard, but resistance to these treatments invariably occurs through various biological mechanisms, such as changes in estrogen receptor activity, mutations in the ESR1 gene, aberrant activation of the PI3K pathway or cell cycle dysregulations. All these factors have led to the development of new therapies, such as selective estrogen receptor degraders (SERDs), or combination therapies with cyclin-dependent kinases (CDK) 4/6 or PI3K inhibitors. Therefore, understanding the estrogen pathway is essential for the treatment and new drug development of hormone-dependent cancers. This mini-review summarizes current literature on the signalization, mechanisms of action and clinical implications of estrogen receptors in breast cancer.

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“…In HR+ tumors we mainly observed resistance patterns in PI3K/Akt pathways, regulation of MAPK cascade, ECM-related pathways, lipid transport and ABC transporters pathways. Indeed, Non-genomic activity of estrogens has been suggested to induce chemoresistance, activating PI3K/AKT and modifying DNA damage response [43]. Resistance patterns emerged in specific subsets of ABC transporters, the ABCA2 family, involved in steroid transport that may regulate breast cancer proliferation and survival, as was suggested in a prostate cancer study [46].…”

Section: Discussionmentioning

confidence: 99%

Chemoresistome Mapping in Individual Breast Cancer Patients Unravels Diversity in Dynamic Transcriptional Adaptation

Dadiani

Friedlander

Perry

et al. 2023

Preprint

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Emerging evidence reinforce the role of non-genetic adaptive resistance to chemotherapy, that involves rewiring of transcriptional programs in surviving tumors. We combined longitudinal transcriptomics with temporal pattern analysis to dissect patient-specific emergence of resistance in breast cancer. Matched triplets of tumor biopsies (pre-treatment, post-treatment and adjacent normal) were collected from breast cancer patients who received neo-adjuvant chemotherapy. Full transcriptome was analyzed by longitudinal pattern classification to follow patient-specific expression modulations. We found that dynamics of gene expression dictates resistance-related modulations. The results unraveled important principles in emergence of adaptive resistance: 1. Genes with resistance patterns are already dysregulated in the primary tumor, supporting a primed drug-tolerant state. 2. In each patient, multiple resistance-related genes are rewired but converge into few dysregulated modules. 3. Rewiring of diverse genes and pathway dysregulation vary among individuals who receive the same treatments. Patient-specific chemoresistome maps disclosed tumors' acquired resistance and exposed their vulnerabilities. Mapping the complexity of dysregulated pathways in individual patients revealed important insights on adaptive resistance mechanisms. To survive the toxic drug effect, tumor cells either sustain a drug-tolerant state or intensify it, specifically bypassing the drug's interference. Depicting an individual road map to resistance can offer personalized therapeutic strategies.

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Non-Genomic Actions of Estrogens on the DNA Repair Pathways Are Associated With Chemotherapy Resistance in Breast Cancer

Cited by 9 publications

References 85 publications

Low-Dose Radiation Can Cause Epigenetic Alterations Associated With Impairments in Both Male and Female Reproductive Cells

Low-Dose Radiation Can Cause Epigenetic Alterations Associated With Impairments in Both Male and Female Reproductive Cells

A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer

Chemoresistome Mapping in Individual Breast Cancer Patients Unravels Diversity in Dynamic Transcriptional Adaptation

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