Tracing anti-cancer and cancer-promoting actions of all-trans retinoic acid in breast cancer to a RARa epigenetic mechanism of mammary epithelial cell fate

Rossetti, Stefano; Ren, Ming; Visconti, Nicolo; Corlazzoli, Francesca; Gagliostro, Vincenzo; Somenzi, Giulia; Yao, Jin; Sun, Yijun; Sacchi, Nicoletta

doi:10.18632/oncotarget.13500

Cited by 11 publications

(21 citation statements)

References 65 publications

(92 reference statements)

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“…It could promote cancer cell apoptosis, scavenging oxygen radicals, inhibit lipid peroxidation, and then as an antioxidant, prevent the deterioration of the tumour5657. All-trans-retinoic acid is involved in retinol metabolism, it could regulate cell proliferation, differentiation, apoptosis, and immune response, and then play an important role in the growth of cancer cells5859. Linoleic acid, as the main substance in arachidonic acid synthesis, is involved in linoleic acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Screening the active compounds of Phellodendri Amurensis cortex for treating prostate cancer by high-throughput chinmedomics

Zhang

Wang

et al. 2017

Sci Rep

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Screening the active compounds of herbal medicines is of importance to modern drug discovery. In this work, an integrative strategy was established to discover the effective compounds and their therapeutic targets using Phellodendri Amurensis cortex (PAC) aimed at inhibiting prostate cancer as a case study. We found that PAC could be inhibited the growth of xenograft tumours of prostate cancer. Global constituents and serum metabolites were analysed by UPLC-MS based on the established chinmedomics analysis method, a total of 54 peaks in the spectrum of PAC were characterised in vitro and 38 peaks were characterised in vivo. Among the 38 compounds characterised in vivo, 29 prototype components were absorbed in serum and nine metabolites were identified in vivo. Thirty-four metabolic biomarkers were related to prostate cancer, and PAC could observably reverse these metabolic biomarkers to their normal level and regulate the disturbed metabolic profile to a healthy state. A chinmedomics approach showed that ten absorbed constituents, as effective compounds, were associated with the therapeutic effect of PAC. In combination with bioactivity assays, the action targets were also predicted and discovered. As an illustrative case study, the strategy was successfully applied to high-throughput screening of active compounds from herbal medicine.

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Section: Discussionmentioning

confidence: 99%

Screening the active compounds of Phellodendri Amurensis cortex for treating prostate cancer by high-throughput chinmedomics

Zhang

Wang

et al. 2017

Sci Rep

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“…Human normal mammary epithelial cells expressing wild type RARA seeded in basement membrane culture providing physiological RA formed 3D acinar structures with a lumen lined by apico-basal polarized cells. Factors affecting the functionality of the RA-RARA mechanism induced 3D amorphous structures with a lumen filled with proliferating cells ( Figure 1 ) [ 88 ]. The inhibition of physiological RA signaling induced aberrant mammary morphogenesis in both mouse and human mammary epithelial cell models and in mouse mammary glands [ 89 , 90 , 91 , 92 ].…”

Section: Ra and Annexins In Mammary Morphogenesis And Breast Cancementioning

confidence: 99%

“…However, T47D cells grown in nude mice fed an RA-enriched diet formed xenograft tumors smaller than xenograft tumors of mice fed a normal diet. In contrast, xenograft tumors of T47D cells carrying a dominant-negative mutant (DN-RARA 403 ) fed the RA-enriched diet were significantly bigger than xenograft tumors of T47D with normal RARA [ 88 ].…”

Section: Ra and Annexins In Mammary Morphogenesis And Breast Cancementioning

confidence: 99%

“…Human isogenic mammary epithelial cell models, such as the MCF10A [ 100 , 101 , 102 , 103 , 104 ] and HME1 [ 88 ] models, revealed a connection between RA-RARA and ANXA8 [ 105 , 106 , 107 , 108 , 109 , 110 ]. The MCF10A cell line derived from a fibrocystic disease of a 36-year-old female was characterized by RARA expression, basal/myoepithelial, luminal markers, and stem/progenitor markers, including aldehyde dehydrogenase isoforms that regulate RA synthesis [ 111 , 112 , 113 ].…”

Section: Ra and Annexins In Mammary Morphogenesis And Breast Cancementioning

confidence: 99%

“…In the course of normal human mammary epithelial cell morphogenesis (left scheme), physiological RA acts as the ancient two-faced Janus Bifrons god that regulates—in a spatiotemporal fashion—cell life (red) and cell death (green). Genetic factors affecting the RA-RARA mechanism induce 3D aberrant mammary morphogenesis (right scheme) [ 88 ].…”

Section: Figurementioning

confidence: 99%

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Emerging Cancer Epigenetic Mechanisms Regulated by All-Trans Retinoic Acid

Rossetti

Sacchi

2020

Cancers

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All-trans retinoic acid (RA), which is the dietary bioactive derivative obtained from animal (retinol) and plant sources (beta-carotene), is a physiological lipid signal of both embryonic and postembryonic development. During pregnancy, either RA deficiency or an excessive RA intake is teratogenic. Too low or too high RA affects not only prenatal, but also postnatal, developmental processes such as myelopoiesis and mammary gland morphogenesis. In this review, we mostly focus on emerging RA-regulated epigenetic mechanisms involving RA receptor alpha (RARA) and Annexin A8 (ANXA8), which is a member of the Annexin family, as well as ANXA8 regulatory microRNAs (miRNAs). The first cancer showing ANXA8 upregulation was reported in acute promyelocytic leukemia (APL), which induces the differentiation arrest of promyelocytes due to defective RA signaling caused by RARA fusion genes as the PML-RARA gene. Over the years, ANXA8 has also been found to be upregulated in other cancers, even in the absence of RARA fusion genes. Mechanistic studies on human mammary cells and mammary glands of mice showed that ANXA8 upregulation is caused by genetic mutations affecting RARA functions. Although not all of the underlying mechanisms of ANXA8 upregulation have been elucidated, the interdependence of RA-RARA and ANXA8 seems to play a relevant role in some normal and tumorigenic settings.

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