Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner

Lin, Yiwei; Kang, Tiebang; Zhou, Binhua P.

doi:10.4161/cc.28619

Cited by 32 publications

(25 citation statements)

References 46 publications

(55 reference statements)

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“…Bmf ) and proliferation (e.g. Aurka ) were apparent in cDKO T cells, none included known Snail targets such as Puma , Mmac1 (PTEN), Cdkn3b (p15ink4b) or Cdkn1a (p21 WAF/CIP1 ) indicative of novel regulatory mechanisms for these factors in T cell biology[15, 61, 62]. However, an in depth comparison of WT and cDKO T cell activation responses as a whole will be needed to better understand the apparent deficit of cDKO T cell “activation”.…”

Section: Discussionmentioning

confidence: 99%

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

et al. 2016

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T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8α+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology.

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Section: Discussionmentioning

confidence: 99%

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

et al. 2016

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“…97,325 Interestingly, the chemotherapeutic drug doxorubicin has the opposite effect, enhancing the interaction between SNAI1 and KDM1A by inducing poly(ADP-ribosyl)ation of SNAI1. 327 The authors further suggest that this increased interaction causes repression of the tumor-supressor gene, PTEN, and may facilitate drugresistance in cancer. SNAI1 also coprecipitates the core KDM1A/CoREST/ HDAC complex, as well as several auxiliary proteins such as HMG20A/B and PHF21A, which are associated with the REST complex, and CtBP, GSE1, and several zinc finger proteins, which are associated with the CtBP complex.…”

Section: Snag Family Proteins Interact With Kdm1a Using Product Mimicrymentioning

confidence: 99%

KDM1 class flavin‐dependent protein lysine demethylases

et al. 2015

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Flavin-dependent, lysine-specific protein demethylases (KDM1s) are a subfamily of amine oxidases that catalyze the selective posttranslational oxidative demethylation of methyllysine side chains within protein and peptide substrates. KDM1s participate in the widespread epigenetic regulation of both normal and disease state transcriptional programs. Their activities are central to various cellular functions, such as hematopoietic and neuronal differentiation, cancer proliferation and metastasis, and viral lytic replication and establishment of latency. Interestingly, KDM1s function as catalytic subunits within complexes with coregulatory molecules that modulate enzymatic activity of the demethylases and coordinate their access to specific substrates at distinct sites within the cell and chromatin. Although several classes of KDM1 -selective small molecule inhibitors have been recently developed, these pan-active site inhibition strategies lack the ability to selectively discriminate between KDM1 activity in specific, and occasionally opposing, functional contexts within these complexes. Here we review the discovery of this class of demethylases, their structures, chemical mechanisms, and specificity. Additionally, we review inhibition of this class of enzymes as well as emerging interactions with coregulatory molecules that regulate demethylase activity in highly specific functional contexts of biological and potential therapeutic importance.

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“…We have shown that RKIP induction in NHL cell lines by the LF-603 αnti-CD20 mAb co-exists with upregulation of the tumor suppressor phosphatase and tensin homologue (PTEN) and Snail/YY1 inhibition, resulting in tumor immune-sensitization [74]. As PTEN is an endogenous inhibitor of the PI3K/Akt signaling [214] and it is transcriptionally repressed by Snail [215], we suggest that RKIP-mediated NF-κB/YY1/Snail inhibition may trigger Akt inactivation by PTEN induction, leading to subsequent reversal of the resistant tumor phenotype.…”

Section: Rkip As a Chemo-immuno-radio-therapeutic Sensitizer In Camentioning

confidence: 99%

RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact

Zaravinos

Bonavida

Chatzaki

et al. 2018

Cancers

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RAF-kinase inhibitor protein (RKIP) is a well-established tumor suppressor that is frequently downregulated in a plethora of solid and hematological malignancies. RKIP exerts antimetastatic and pro-apoptotic properties in cancer cells, via modulation of signaling pathways and gene products involved in tumor survival and spread. Here we review the contribution of RKIP in the regulation of early metastatic steps such as epithelial–mesenchymal transition (EMT), migration, and invasion, as well as in tumor sensitivity to conventional therapeutics and immuno-mediated cytotoxicity. We further provide updated justification for targeting RKIP as a strategy to overcome tumor chemo/immuno-resistance and suppress metastasis, through the use of agents able to modulate RKIP expression in cancer cells.

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Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner

Cited by 32 publications

References 46 publications

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

KDM1 class flavin‐dependent protein lysine demethylases

RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact

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