Hes3 Enhances the Malignant Phenotype of Lung Cancer through Upregulating Cyclin D1, Cyclin D3 and MMP7 Expression

Fang, Changqing; Jiang, Bao-guo; Shi, Xiuying; Fan, Chuifeng

doi:10.7150/ijms.28139

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…It is possible that multiple cellular mechanisms might mediate anticancer effects via either HES3 siRNA or the small molecules we identified. Hes3 RNA interference leads to the death of multiple cell types (3,34), and recently, Hes3 was implicated in the regulation of cell proliferation and cell invasion in lung cancer cell lines (49). Our observation that cell mechanics-related GO terms were strongly featured in the PC analysis is consistent with the latter point.…”

Section: Roles Of Hes3 In Regeneration and Cancersupporting

confidence: 88%

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

et al. 2019

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Cancer cells can switch between signaling pathways to regulate growth under different conditions. In the tumor microenvironment, this likely helps them evade therapies that target specific pathways. We must identify all possible states and utilize them in drug screening programs. One such state is characterized by expression of the transcription factor Hairy and Enhancer of Split 3 (HES3) and sensitivity to HES3 knockdown, and it can be modeled in vitro. Here, we cultured 3 primary human brain cancer cell lines under 3 different culture conditions that maintain low, medium, and high HES3 expression and characterized gene regulation and mechanical phenotype in these states. We assessed gene expression regulation following HES3 knockdown in the HES3‐high conditions. We then employed a commonly used human brain tumor cell line to screen Food and Drug Administration (FDA)‐approved compounds that specifically target the HES3‐high state. We report that cells from multiple patients behave similarly when placed under distinct culture conditions. We identified 37 FDA‐approved compounds that specifically kill cancer cells in the high‐HES3–expression conditions. Our work reveals a novel signaling state in cancer, biomarkers, a strategy to identify treatments against it, and a set of putative drugs for potential repurposing.—Poser, S. W., Otto, O., Arps‐Forker, C., Ge, Y., Herbig, M., Andree, C., Gruetzmann, K., Adasme, M. F., Stodolak, S., Nikolakopoulou, P., Park, D. M., Mcintyre, A., Lesche, M., Dahl, A., Lennig, P., Bornstein, S. R., Schroeck, E., Klink, B., Leker, R. R., Bickle, M., Chrousos, G. P., Schroeder, M., Cannistraci, C. V., Guck, J., Androutsellis‐Theotokis, A. Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery. FASEB J. 33, 9235–9249 (2019). http://www.fasebj.org

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Section: Roles Of Hes3 In Regeneration and Cancersupporting

confidence: 88%

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

et al. 2019

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“… 28 Further, human HES3 has been shown to increase malignancy in lung cancer. 29 Similarly, human HES6 has been shown to not only act as an inhibitor of HES1 (and thus promote neuronal differentiation), but also promote aggressiveness in multiple cancers including prostate and colorectal. 30 , 31 , 32 Hes4 drives osteogenesis and inhibits adipogenesis by inhibiting Twist-1.…”

Section: Overview Of Notch Signalingmentioning

confidence: 99%

Notch signaling: Its essential roles in bone and craniofacial development

et al. 2021

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Notch is a cell–cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.

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“…The previous evidence provided important information that c-myc controlled cancer cell proliferation, and c-myc was associated with unfavorable survival of lung cancer patients (35). A vitro study con rmed that overexpression of Cyclin D1 promoted lung cancer cell proliferation and invasion (36). Cyclin D1 also was identi ed to activate the occurrence of EMT.…”

Section: Discussionmentioning

confidence: 95%

Down-Regulated MAC30 Suppresses Lung Cancer Invasion and EMT by Inhibiting Wnt/β-Catenin Signaling Pathway

Zhou

Ji²,

chen

et al. 2021

Preprint

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Backgrounds：Over-expressed meningioma-associated protein (MAC30) was proved to be a biomarker for worse prognosis in non–small cell lung cancer (NSCLC). However, the regulated mechanism of MAC30 in epithelial–mesenchymal transition (EMT) and lung cancer invasion is unknown. Methods：Transformed growth factor (TGF-β) was used to induce EMT in A549 cells in vitro. MAC30 siRNA was transfected into cells to silence the gene expression. Real-Time PCR was prepared to assess the levels of MAC30 mRNA. Methyl thiazolyl tetrazolium (MTT) and Transwell invasion assays were performed to study the proliferation and invasion of A549 cells. Expression of MAC30, EMT-related proteins, Wnt/β-catenin signal and its downstream factors were explored by ELISA. Results: We found enhanced MAC30 expression in A549 cells. MAC30 Knockdown inhibited TGF-β-induced lung cell proliferation and invasion. Furthermore, elevated levels of mesenchymal markers (N-cadherin, vimentin) and decreased levels of epithelial markers E-cadherin in A549 cells with TGF-β incubation were reversed by MAC30 siRNA. Finally, MAC30 knockdown significantly suppressed TGF-β-upregulated protein levels of Wnt/ β-catenin signaling and its downstream genes (surviving, c-myc and cyclin D1). Conclusions: We firstly confirm that MAC30 knockdown limits lung cancer growth and EMT through inhibiting the activation of Wnt/β-catenin pathway.

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Hes3 Enhances the Malignant Phenotype of Lung Cancer through Upregulating Cyclin D1, Cyclin D3 and MMP7 Expression

Cited by 9 publications

References 20 publications

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

Notch signaling: Its essential roles in bone and craniofacial development

Down-Regulated MAC30 Suppresses Lung Cancer Invasion and EMT by Inhibiting Wnt/β-Catenin Signaling Pathway

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