The role of SET/I2PP2A in canine mammary tumors

Kake, Satoru; Tsuji, Shunya; Enjoji, Shuhei; Hanasaki, Sayaka; Hayase, Hiroshi; Yabe, Ryotaro; Tanaka, Yuiko; Nakagawa, Takayuki; Liu, Hao‐Ping; Chang, Shih‐Chieh; Usui, Tatsuya; Sato, Koichi

doi:10.1038/s41598-017-04291-7

Cited by 10 publications

(17 citation statements)

References 37 publications

(51 reference statements)

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“…We and others have reported previously that SET KD suppressed Akt signaling (13,24), ERK1/2 signaling (24), mTOR signaling (25), NFkB signaling, and b-catenin signaling (26). However, we observed that SET KD did not have a marked effect on these cell-signaling molecules in MKN45 cells ( Fig.…”

Section: Set/i2pp2a Associates With Pp2a-b56 Complex and Stabilizes Econtrasting

confidence: 45%

Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis

Enjoji

Yabe

Tsuji

et al. 2018

Molecular Cancer Research

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Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possesses the ability to self-renew and dedifferentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown. Increased kinase and decreased phosphatase activity are hallmarks of oncogenic signaling. Protein phosphatase 2A (PP2A) functions as a tumor-suppressor enzyme, and elevated levels of SET/I2PP2A, an endogenous PP2A protein inhibitor, are correlated with poor prognosis of several human cancers. Here, it was determined that SET expression was elevated in tumor tissue in a gastric cancer mouse model system, and SET expression was positively correlated with poor survival of human gastric cancer patients. Mechanistically, SET knockdown decreased E2F1 levels and suppressed the stemness of cancer cell lines. Immunoprecipitations show SET associated with the PP2A-B56 complex, and the B56 subunit interacted with the E2F1 transcription factor. Treatment of gastric cancer cells with the SET-targeting drug OP449 increased PP2A activity, decreased E2F1 protein levels, and suppressed stemness of cancer cells. These data indicate that a SET/PP2A/E2F1 axis regulates cancer cell stemness and is a potential target for gastric cancer therapy. This study highlights the oncogenic role of SET/I2PP2A in gastric cancer and suggests that SET maintains cancer cell stemness by suppressing PP2A activity and stabilizing E2F1. .

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Section: Set/i2pp2a Associates With Pp2a-b56 Complex and Stabilizes Econtrasting

confidence: 45%

Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis

Enjoji

Yabe

Tsuji

et al. 2018

Molecular Cancer Research

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“…The nature of HRV dynamics is the object of lively debates (Glass, 2009 ; Sassi et al, 2009 ; Valenza et al, 2017 ). The question of whether or not the normal heart rate is chaotic (Glass, 2009 ) is leading investigators to refine the concept of complexity variability using the tools of non-linear dynamics (Valenza et al, 2017 ) and to restate the multifractal nature of heart rate variability (Sassi et al, 2009 ). We focus on the important role of crucial events , advocated in 2002 by Allegrini et al ( 2002 ).…”

Section: Future Directionsmentioning

confidence: 99%

Meditation-Induced Coherence and Crucial Events

et al. 2018

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In this paper we emphasize that 1/f noise has two different origins, one compatible with Laplace determinism and one determined by unpredictable crucial events. The dynamics of heartbeats, manifest as heart rate variability (HRV) time series, are determined by the joint action of these different memory sources with meditation turning the Laplace memory into a strongly coherent process while exerting an action on the crucial events favoring the transition from the condition of ideal 1/f noise to the Gaussian basin of attraction. This theoretical development affords a method of statistical analysis that establishes a quantitative approach to the evaluation of the stress reduction realized by the practice of Chi meditation and Kundalini Yoga.

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“…Inhibition of SET methyltransferase by shRNA and FTY720, reported to directly interact with SET proteins, suppressed cell proliferation, colony formation, and in vivo tumor growth of canine mammary and osteosarcoma cell lines. Furthermore, SET knockdown repressed mTOR and NF-kB signaling in both types of canine cancer (223,224). Using BB-Cl-Amidine (BB-CLA) to inhibit protein-arginine deiminases (PADs) resulted in the decrease of viability and tumorigenicity of FIGURE 3 | Effects of some alternative epigenetic inhibitors in canine mammary cancer cells.…”

Section: Alternative Epigenetic Targetsmentioning

confidence: 99%

Epigenetic Mechanisms in Canine Cancer

2020

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A plethora of data has highlighted the role of epigenetics in the development of cancer. Initiation and progression of different cancer types are associated with a variety of changes of epigenetic mechanisms, including aberrant DNA methylation, histone modifications, and miRNA expression. At the same time, advances in the available epigenetic tools allow to investigate and reverse these epigenetic changes and form the basis for the development of anticancer drugs in human oncology. Although human and canine cancer shares several common features, only recently that studies emerged investigating the epigenetic landscape in canine cancer and applying epigenetic modulators to canine cancer. This review focuses on the existing studies involving epigenetic changes in different types of canine cancer and the use of small-molecule inhibitors in canine cancer cells.

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The role of SET/I2PP2A in canine mammary tumors

Cited by 10 publications

References 37 publications

Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis

Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis

Meditation-Induced Coherence and Crucial Events

Epigenetic Mechanisms in Canine Cancer

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