Chemotherapy-induced S100A10 recruits KDM6A to facilitate OCT4-mediated breast cancer stemness

Lu, Haiquan; Xie, Yangyiran; Tran, Thi Thanh Van; Lan, Jie; Yang, Yongkang; Murugan, Naveena L.; Wang, Ru; Wang, Yueyang J.; Semenza, Gregg L.

doi:10.1172/jci138577

Cited by 95 publications

(78 citation statements)

References 77 publications

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“…It is reported that histone demethylase can activate SOX2 expression through histone demethylation. 16 SOX2 is considered to be an oncogene in LCA. 17,18 RT-qPCR found that SOX2 was highly expressed in LCA ( Figure 6A).…”

Section: Kdm5b Promoted Sox2 Expressionmentioning

confidence: 99%

<p>microRNA-139-3p Inhibits Malignant Behaviors of Laryngeal Cancer Cells via the KDM5B/SOX2 Axis and the Wnt/β-Catenin Pathway</p>

Ma¹,

Chen²,

Yu³

2020

CMAR

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Background: Laryngeal cancer (LCA) is a common head and neck cancer. Lysine demethylase 5B (KDM5B) knockdown is expected as a new target for cancer prevention. We investigated the molecular mechanism of KDM5B in LCA. Materials and Methods: The levels of KDM5B, microRNA (miR)-139-3p and highmobility-group box 2 (SOX2) in LCA tissues and cells, normal tissues and cells were detected. The effect of KDM5B on LCA was evaluated. The upstream miR of KDM5B and the downstream gene and pathway of KDM5B were predicted and their effects on LCA were analyzed. The Wnt/β-catenin pathway-specific activator agonist was delivered into LCA cells expressing miR-139-3p mimic to evaluate the role of the Wnt/β-catenin pathway. Results: KDM5B was highly expressed in LCA, and inhibition of KDM5B suppressed LCA progression. miR-139-3p, downregulated in LCA tissues, was a regulatory miR of KDM5B. Overexpression of miR-139-3p significantly inhibited the malignant biological behaviors of LCA cells. KDM5B promoted SOX2 expression via histone demethylation. SOX2 was highly expressed in LCA, and overexpression of SOX2 promoted LCA progression by inducing the Wnt/β-catenin pathway. Activated Wnt/β-catenin pathway attenuated the inhibitory effect of miR-139-3p mimic on the malignant biological behaviors of LCA cells. Conclusion: miR-139-3p overexpression inhibited LCA development via regulating the KDM5B/SOX2 axis and inhibiting the Wnt/β-catenin pathway.

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Section: Kdm5b Promoted Sox2 Expressionmentioning

confidence: 99%

<p>microRNA-139-3p Inhibits Malignant Behaviors of Laryngeal Cancer Cells via the KDM5B/SOX2 Axis and the Wnt/β-Catenin Pathway</p>

Ma¹,

Chen²,

Yu³

2020

CMAR

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“…The classical CSC model proposes that tumor heterogeneity arises from CSCs that transit through different states (epithelial and mesenchymal) of stemness and differentiation (CPCs and CDCs) by unidirectional conversion from CSCs to non-CSCs ( Singh et al, 2015 ). This model, where CSCs would be at the apex of the process, might better account for heterogeneity and hierarchy of cells in the same tumor, but it does not account for recent reports showing that non-CSCs might revert to CSCs ( Chaffer et al, 2011 ; Gupta et al, 2011 ; Kim et al, 2013 ; Singh et al, 2015 ; Lu et al, 2020 ). The plastic CSC model proposes that bidirectional conversions are possible between CSCs and non-CSCs, suggesting that during the tumor process, non-CSCs might be induced into CSCs, thus creating new tumor populations ( Chaffer et al, 2011 ; Kim et al, 2013 ; Singh et al, 2015 ; Lu et al, 2020 ).…”

Section: Cell Heterogeneity Hierarchy and Plasticity In Cancermentioning

confidence: 91%

“…The plasticity of non-CSCs reverting to a CSC state might be made possible by the genetic instability caused by the absence of genomic homeostasis in the i-CSC/CSC 0 and handed down throughout all its progeny, including CDCs. This instability would allow non-CSCs to be de novo reactivated (neo-re-programmed) in their pluripotency gene regulatory network (OCT4, SOX2, NANONG, KLF4, MYC) by endogenous, niche and/or microenvironmental signals, probably in a different way from the original i-CSC/CSC 0 , thus generating new tumor cell populations ( Iliopulos et al, 2011 ; Kim et al, 2013 ; Cabrera et al, 2015 ; Singh et al, 2015 ; Yang et al, 2018 ; Lu et al, 2020 ). Depending on its genetic, epigenetic and microenvironment conditions, a tumor cell could thus realize a defined genic program (“inductive gene chain”) that confers specific phenotypic and physio-pathological features, responsible for a peculiar cell heterogeneity and hierarchy.…”

Section: Cell Heterogeneity Hierarchy and Plasticity In Cancermentioning

confidence: 99%

Defined Mathematical Relationships Among Cancer Cells Suggest Modular Growth in Tumor Progression and Highlight Developmental Features Consistent With a Para-Embryonic Nature of Cancer

Manzo

2020

Front. Cell Dev. Biol.

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Several similarities between the embryo development and the cancer process suggest the para-embryonic nature of tumors. Starting from an initial cancer stem cell (i-CSC) as a para-embryonic stem cell (p-ESC), a hierarchic sequence of CSCs (CSC 1 s, CSC 2 s, CSC 3 s) and non-CSCs [cancer progenitor cells (CPCs), cancer differentiated cells (CDCs)] would be generated, mimicking an ectopic rudimentary ontogenesis. Such a proposed heterogeneous cell hierarchy within the tumor structure would suggest a tumor growth model consistent with experimental data reported for mammary tumors. By tabulating the theoretical data according to this model, it is possible to identify defined mathematical relationships between cancer cells (CSCs and non-CSCs) that are surprisingly similar to experimental data. Moreover, starting from this model, it is possible to speculate that, during progression, tumor growth would occur in a modular way that recalls the propagation of tumor spheres in vitro . All these considerations favor a comparison among normal blastocysts (as in vitro embryos), initial avascular tumors (as in vivo abnormal blastocysts) and tumor spheres (as in vitro abnormal blastocysts). In conclusion, this work provides further support for the para-embryonic nature of the cancer process, as recently theorized.

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“…c-Myc is important for regulating proliferation and the survival of glioma cancer stem cell [ 23 ]. Oct4 is responsible for breast CSC specification and regulated Nanog, Sox2 and Klf4 gene [ 24 ]. Sox2 drives cancer stemness and fuels tumor initiation [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

6-Methoxymellein Isolated from Carrot (Daucus carota L.) Targets Breast Cancer Stem Cells by Regulating NF-κB Signaling

et al. 2020

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The presence of breast cancer stem cells (BCSCs) induces the aggressive progression and recurrence of breast cancer. These cells are drug resistant, have the capacity to self-renew and differentiate and are involved in recurrence and metastasis, suggesting that targeting BCSCs may improve treatment efficacy. In this report, methanol extracts of carrot root were purified by means of silica gel, Sephadex LH-20, and preparative high-performance liquid chromatography to isolate a compound targeting mammosphere formation. We isolated the compound 6-methoxymellein, which inhibits the proliferation and migration of breast cancer cells, reduces mammosphere growth, decreases the proportion of CD44+/CD24− cells in breast cancer cells and decreases the expression of stemness-associated proteins c-Myc, Sox-2 and Oct4. 6-Methoxymellein reduces the nuclear localization of nuclear factor-κB (NF-κB) subunit p65 and p50. Subsequently, 6-methoxymellein decreases the mRNA transcription and secretion of IL-6 and IL-8. Our data suggest that 6-methoxymellein may be an anticancer agent that inhibits BCSCs via NF-κB/IL-6 and IL-8 regulation.

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Chemotherapy-induced S100A10 recruits KDM6A to facilitate OCT4-mediated breast cancer stemness

Cited by 95 publications

References 77 publications

<p>microRNA-139-3p Inhibits Malignant Behaviors of Laryngeal Cancer Cells via the KDM5B/SOX2 Axis and the Wnt/β-Catenin Pathway</p>

<p>microRNA-139-3p Inhibits Malignant Behaviors of Laryngeal Cancer Cells via the KDM5B/SOX2 Axis and the Wnt/β-Catenin Pathway</p>

Defined Mathematical Relationships Among Cancer Cells Suggest Modular Growth in Tumor Progression and Highlight Developmental Features Consistent With a Para-Embryonic Nature of Cancer

6-Methoxymellein Isolated from Carrot (Daucus carota L.) Targets Breast Cancer Stem Cells by Regulating NF-κB Signaling

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