40 TGFβ receptor inhibitors target the CD44high/Id1high glioma stem cell population in human glioblastoma

Anido, Judit; Sáez-Borderías, Andrea; Gonzàlez-Juncà, Alba; Folch, Gerard; Prieto-Sánchez, Rosa M.; Cuartas, Isabel; Raventós, C.; Seoane, Joan

doi:10.1016/s1359-6349(10)70849-1

Cited by 2 publications

(2 citation statements)

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“…ID1 is a key TGFβ target gene that mediates the oncogenic effects of TGFβ 22 , 25 , 57 , 58 . It is widely thought that TGFβ signaling increases ID1 abundance at the mRNA level 57 . Here, we show that TGFβ also upregulates ID1 expression post-translationally through inhibiting its ubiquitin-mediated degradation, providing an unidentified mechanism for TGFβ-induced upregulation of ID1.…”

Section: Discussionmentioning

confidence: 99%

Interplay between transforming growth factor-β and Nur77 in dual regulations of inhibitor of differentiation 1 for colonic tumorigenesis

Niu

Liu

et al. 2021

Nat Commun

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The paradoxical roles of transforming growth factor-β (TGFβ) signaling and nuclear receptor Nur77 in colon cancer development are known but the underlying mechanisms remain obscure. Inhibitor of differentiation 1 (ID1) is a target gene of TGFβ and a key promoter for colon cancer progression. Here, we show that Nur77 enhances TGFβ/Smad3-induced ID1 mRNA expression through hindering Smurf2-mediated Smad3 mono-ubiquitylation, resulting in ID1 upregulation. In the absence of TGFβ, however, Nur77 destabilizes ID1 protein by promoting Smurf2-mediated ID1 poly-ubiquitylation, resulting in ID1 downregulation. Interestingly, TGFβ stabilizes ID1 protein by switching Nur77 interaction partners to inhibit ID1 ubiquitylation. This also endows TGFβ with an active pro-tumorigenic action in Smad4-deficient colon cancers. Thus, TGFβ converts Nur77’s role from destabilizing ID1 protein and cancer inhibition to inducing ID1 mRNA expression and cancer promotion, which is highly relevant to colon cancer stemness, metastasis and oxaliplatin resistance. Our data therefore define the integrated duality of Nur77 and TGFβ signaling in regulating ID1 expression and provide mechanistic insights into the paradoxical roles of TGFβ and Nur77 in colon cancer progression.

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Section: Discussionmentioning

confidence: 99%

Interplay between transforming growth factor-β and Nur77 in dual regulations of inhibitor of differentiation 1 for colonic tumorigenesis

Niu

Liu

et al. 2021

Nat Commun

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“…Zhang et al (2011) showed that a blockade of TGF-b signaling by the TGFBR1 kinase inhibitor LY2109761 enhances the response to radiation and prolongs survival in glioblastoma patients. Anido et al (2010) showed that TGFb receptor inhibitors target the CD44(high)/Id1(high) glioma-initiating cell population in human glioblastoma. Future studies are warranted to further explore the possibilities of using miR-127-3p and SKI as targets for glioma therapy.…”

Section: Discussionmentioning

confidence: 99%

Next Generation Sequencing Analysis of miRNAs: MiR-127-3p Inhibits Glioblastoma Proliferation and Activates TGF-β Signaling by Targeting SKI

Jiang

Jin

Liu

et al. 2014

OMICS: A Journal of Integrative Biology

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Glioblastoma (GBM) proliferation is a multistep process during which the expression levels of many genes that control cell proliferation, cell death, and genetic stability are altered. MicroRNAs (miRNAs) are emerging as important modulators of cellular signaling, including cell proliferation in cancer. In this study, using next generation sequencing analysis of miRNAs, we found that miR-127-3p was downregulated in GBM tissues compared with normal brain tissues; we validated this result by RT-PCR. We further showed that DNA demethylation and histone deacetylase inhibition resulted in downregulation of miR-127-3p. We demonstrated that miR-127-3p overexpression inhibited GBM cell growth by inducing G1-phase arrest both in vitro and in vivo. We showed that miR-127-3p targeted SKI (v-ski sarcoma viral oncogene homolog [avian]), RGMA (RGM domain family, member A), ZWINT (ZW10 interactor, kinetochore protein), SERPINB9 (serpin peptidase inhibitor, clade B [ovalbumin], member 9), and SFRP1 (secreted frizzled-related protein 1). Finally, we found that miR-127-3p suppressed GBM cell growth by inhibiting tumor-promoting SKI and activating the tumor suppression effect of transforming growth factor-b (TGF-b) signaling. This study showed, for the first time, that miR-127-3p and its targeted gene SKI, play important roles in GBM and may serve as potential targets for GBM therapy.

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40 TGFβ receptor inhibitors target the CD44high/Id1high glioma stem cell population in human glioblastoma

Cited by 2 publications

References 0 publications

Interplay between transforming growth factor-β and Nur77 in dual regulations of inhibitor of differentiation 1 for colonic tumorigenesis

Interplay between transforming growth factor-β and Nur77 in dual regulations of inhibitor of differentiation 1 for colonic tumorigenesis

Next Generation Sequencing Analysis of miRNAs: MiR-127-3p Inhibits Glioblastoma Proliferation and Activates TGF-β Signaling by Targeting SKI

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