Left-Right Asymmetry in Embryonic Development and Breast Cancer: Common Molecular Determinants?

DNA methylation (5-methylcytosine, 5mC) was once viewed as a stable epigenetic modification until Rao and colleagues identified Ten-eleven translocation 1 (TET1) as the first 5mC dioxygenase in 2009. TET family genes (including TET1, TET2, and TET3) encode proteins that can catalyze 5mC oxidation and consequently modulate DNA methylation, not only regulating embryonic development and cellular differentiation, but also playing critical roles in various physiological and pathophysiological processes. Soon after the discovery of TET family 5mC dioxygenases, aberrant 5mC oxidation and dysregulation of TET family genes have been reported in breast cancer as well as other malignancies. The impacts of aberrant 5mC oxidation and dysregulated TET family genes on the different aspects (so-called cancer hallmarks) of breast cancer have also been extensively investigated in the past decade. In this review, we summarize current understanding of the causes and consequences of aberrant 5mC oxidation in the pathogenesis of breast cancer. The challenges and future perspectives of this field are also discussed.

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Abstract PS7-86: Molecular determinants of racial disparity guide triple-therapy for triple negative breast cancer

10.1158/1538-7445.sabcs20-ps7-86 ◽

2021 ◽

Author(s):

Sumit Siddharth ◽

Sheetal Parida ◽

Nethaji Muniraj ◽

Shawn M Hercules ◽

Arumugam Nagalingam ◽

...

Keyword(s):

Breast Cancer ◽

Triple Therapy ◽

Triple Negative Breast Cancer ◽

Racial Disparity ◽

Triple Negative ◽

Molecular Determinants

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Long-Pentraxin 3 Affects Primary Cilium in Zebrafish Embryo and Cancer Cells via the FGF System

Cancers ◽

10.3390/cancers12071756 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1756

Author(s):

Jessica Guerra ◽

Paola Chiodelli ◽

Chiara Tobia ◽

Claudia Gerri ◽

Marco Presta

Keyword(s):

Embryonic Development ◽

Cancer Cells ◽

Cancer Progression ◽

Primary Cilium ◽

Zebrafish Embryo ◽

Dependent Manner ◽

Pentraxin 3 ◽

Left Right Asymmetry ◽

The Impact ◽

Cilium Length

Primary cilium drives the left-right asymmetry process during embryonic development. Moreover, its dysregulation contributes to cancer progression by affecting various signaling pathways. The fibroblast growth factor (FGF)/FGF receptor (FGFR) system modulates primary cilium length and plays a pivotal role in embryogenesis and tumor growth. Here, we investigated the impact of the natural FGF trap long-pentraxin 3 (PTX3) on the determination of primary cilium extension in zebrafish embryo and cancer cells. The results demonstrate that down modulation of the PTX3 orthologue ptx3b causes the shortening of primary cilium in zebrafish embryo in a FGF-dependent manner, leading to defects in the left-right asymmetry determination. Conversely, PTX3 upregulation causes the elongation of primary cilium in FGF-dependent cancer cells. Previous observations have identified the PTX3-derived small molecule NSC12 as an orally available FGF trap with anticancer effects on FGF-dependent tumors. In keeping with the non-redundant role of the FGF/FGR system in primary cilium length determination, NSC12 induces the elongation of primary cilium in FGF-dependent tumor cells, thus acting as a ciliogenic anticancer molecule in vitro and in vivo. Together, these findings demonstrate the ability of the natural FGF trap PTX3 to exert a modulatory effect on primary cilium in embryonic development and cancer. Moreover, they set the basis for the design of novel ciliogenic drugs with potential implications for the therapy of FGF-dependent tumors.

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Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial—Clinical outcomes and molecular determinants of response

PLoS ONE ◽

10.1371/journal.pone.0210891 ◽

2019 ◽

Vol 14 (2) ◽

pp. e0210891 ◽

Cited By ~ 4

Author(s):

Caitlin Murphy ◽

Andrea Muscat ◽

David Ashley ◽

Violet Mukaro ◽

Linda West ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Outcomes ◽

Phase Ii ◽

Molecular Determinants

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Cell chirality: emergence of asymmetry from cell culture

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2015.0413 ◽

2016 ◽

Vol 371 (1710) ◽

pp. 20150413 ◽

Cited By ~ 17

Author(s):

Leo Q. Wan ◽

Amanda S. Chin ◽

Kathryn E. Worley ◽

Poulomi Ray

Keyword(s):

Cell Culture ◽

Embryonic Development ◽

Birth Defects ◽

Controlled Experiments ◽

Internal Organs ◽

Recent Developments ◽

Living Organisms ◽

Left Right Asymmetry

Increasing evidence suggests that intrinsic cell chirality significantly contributes to the left–right (LR) asymmetry in embryonic development, which is a well-conserved characteristic of living organisms. With animal embryos, several theories have been established, but there are still controversies regarding mechanisms associated with embryonic LR symmetry breaking and the formation of asymmetric internal organs. Recently, in vitro systems have been developed to determine cell chirality and to recapitulate multicellular chiral morphogenesis on a chip. These studies demonstrate that chirality is indeed a universal property of the cell that can be observed with well-controlled experiments such as micropatterning. In this paper, we discuss the possible benefits of these in vitro systems to research in LR asymmetry, categorize available platforms for single-cell chirality and multicellular chiral morphogenesis, and review mathematical models used for in vitro cell chirality and its applications in in vivo embryonic development. These recent developments enable the interrogation of the intracellular machinery in LR axis establishment and accelerate research in birth defects in laterality. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

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