RUNX1–Survivin Axis Is a Novel Therapeutic Target for Malignant Rhabdoid Tumors

Mikami, Masamitsu; Masuda, Tatsuya; Kanatani, Takuya; Noura, Mina; Umeda, Katsutsugu; Hiramatsu, Hidefumi; Kubota, Hirohito; Daifu, Tomoo; Iwai, Atsushi; Hattori, Etsuko; Furuichi, Kana; Takasaki, Saho; Tanaka, Sunao; Matsui, Yasuhisa; Matsuo, Hidemasa; Hirata, Masahiro; Kataoka, Tatsuki R.; Nakahata, Tatsutoshi; Kuwahara, Yasumichi; Iehara, Tomoko; Hosoi, Hajime; Imai, Yumiko; Takita, Junko; Sugiyama, Hiroshi; Adachi, Souichi; Kamikubo, Yasuhiko

doi:10.14348/molcells.2022.2031

Cited by 2 publications

(1 citation statement)

References 36 publications

(62 reference statements)

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“…Survivin expression is tightly regulated by multiple manners. Survivin is regulated by p53, runt-related transcription factor 1, specificity protein 1, TGF-β, and HIF-1α at the transcriptional level 55 , 56 . Furthermore, survivin expression has been reported to be regulated by NF-κB, MAPK/ERK, and JAK/STAT signaling pathways 57 , 58 .…”

Section: Discussionmentioning

confidence: 99%

TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance

Liao,

Qing,

et al. 2024

Int. J. Biol. Sci.

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Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. Despite continuous improvement in treatment strategies, recurrence or persistence of cancer after radiotherapy is still inevitable, highlighting the need to identify therapeutic resistance factors and develop effective methods for NPC treatment. Herein, we found that TRAF4 is overexpressed in NPC cells and tissues. Knockdown TRAF4 significantly increased the radiosensitivity of NPC cells, possibly by inhibiting the Akt/Wee1/CDK1 axis, thereby suppressing survivin phosphorylation and promoting its degradation by FBXL7. TRAF4 is positively correlated with p-Akt and survivin in NPC tissues. High protein levels of TRAF4 were observed in acquired radioresistant NPC cells, and knockdown of TRAF4 overcomes radioresistant in vitro and the xenograft mouse model. Altogether, our study highlights the TRAF4-survivin axis as a potential therapeutic target for radiosensitization in NPC.

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Section: Discussionmentioning

confidence: 99%

TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance

Liao,

Qing,

et al. 2024

Int. J. Biol. Sci.

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Targeting cis-regulatory elements of FOXO family is a novel therapeutic strategy for induction of leukemia cell differentiation

Kurayoshi,

Takase,

Ueno

et al. 2023

Cell Death Dis

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Differentiation therapy has been proposed as a promising therapeutic strategy for acute myeloid leukemia (AML); thus, the development of more versatile methodologies that are applicable to a wide range of AML subtypes is desired. Although the FOXOs transcription factor represents a promising drug target for differentiation therapy, the efficacy of FOXO inhibitors is limited in vivo. Here, we show that pharmacological inhibition of a common cis-regulatory element of forkhead box O (FOXO) family members successfully induced cell differentiation in various AML cell lines. Through gene expression profiling and differentiation marker-based CRISPR/Cas9 screening, we identified TRIB1, a complement of the COP1 ubiquitin ligase complex, as a functional FOXO downstream gene maintaining an undifferentiated status. TRIB1 is direct target of FOXO3 and the FOXO-binding cis-regulatory element in the TRIB1 promoter, referred to as the FOXO-responsive element in the TRIB1 promoter (FRE-T), played a critical role in differentiation blockade. Thus, we designed a DNA-binding pharmacological inhibitor of the FOXO-FRE-T interface using pyrrole-imidazole polyamides (PIPs) that specifically bind to FRE-T (FRE-PIPs). The FRE-PIPs conjugated to chlorambucil (FRE-chb) inhibited transcription of TRIB1, causing differentiation in various AML cell lines. FRE-chb suppressed the formation of colonies derived from AML cell lines but not from normal counterparts. Administration of FRE-chb inhibited tumor progression in vivo without remarkable adverse effects. In conclusion, targeting cis-regulatory elements of the FOXO family is a promising therapeutic strategy that induces AML cell differentiation.

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RUNX1–Survivin Axis Is a Novel Therapeutic Target for Malignant Rhabdoid Tumors

Cited by 2 publications

References 36 publications

TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance

TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance

Targeting cis-regulatory elements of FOXO family is a novel therapeutic strategy for induction of leukemia cell differentiation

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