https://doi.org/10.4081/ejh.2021.3255
Downregulation of Williams syndrome transcription factor (WSTF) suppresses glioblastoma cell growth and invasion by inhibiting PI3K/AKT signal pathway
Submitted: 25 March 2021
Accepted: 23 October 2021
Published: 17 November 2021
Accepted: 23 October 2021
Abstract Views: 613
PDF: 412
HTML: 30
HTML: 30
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Williams syndrome transcription factor (WSTF) participates in diverse cellular processes, including tumor cell proliferation and migration. However, the function of WSTF in glioblastoma (GBM) remains unknown. Data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) datasets showed that WSTF was up-regulated in GBM tissues. Moreover, WSTF was also increased in the GBM cells. pcDNA-mediated over-expression of WSTF contributed to cell proliferation and invasion of GBM cells, while GBM cell proliferation and invasion were suppressed by shRNA-mediated silencing of WSTF. Additionally, GBM cell apoptosis was reduced by over-expression of WSTF accompanied by decrease in Bax and cleaved caspase-3, while promoted by silencing of WSTF with increase in Bax and cleaved caspase-3. Protein expression of AKT phosphorylation was enhanced by WSTF over-expression while reduced by WSTF silencing. Inhibitor of phosphatidylinositol 3 kinase attenuated WSTF over-expression-induced increase in GBM cell proliferation and invasion. In conclusion, WSTF contributed to GBM cell growth and invasion through activation of PI3K/AKT pathway.
Lah TT, Novak M, Breznik B. Brain malignancies: Glioblastoma and brain metastases. Semin Cancer Biol 2020;60:262-73.
DOI: https://doi.org/10.1016/j.semcancer.2019.10.010
Campos B, Olsen LR, Urup T, Poulsen HS. A comprehensive profile of recurrent glioblastoma. Oncogene 2016;35:5819-25.
DOI: https://doi.org/10.1038/onc.2016.85
Jiang P, Mukthavavam R, Chao Y, Bharati IS, Fogal V, Pastorino S, et al. Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs. J Transl Med 2014;12:13.
DOI: https://doi.org/10.1186/1479-5876-12-13
Cho KS, Elizondo LI, Boerkoel CF. Advances in chromatin remodeling and human disease. Curr Opin Genet Dev 2004;14:308-15.
DOI: https://doi.org/10.1016/j.gde.2004.04.015
Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, et al. WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 2009;457:57-62.
DOI: https://doi.org/10.1038/nature07668
Culver-Cochran AE, Chadwick BP. Loss of WSTF results in spontaneous fluctuations of heterochromatin formation and resolution, combined with substantial changes to gene expression. BMC Genomics 2013;14:740.
DOI: https://doi.org/10.1186/1471-2164-14-740
Aydin ÖZ, Marteijn JA, Ribeiro-Silva C, Rodríguez López A, Wijgers N, Smeenk G, et al. Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription. Nucleic Acids Res 2014;42:8473-85.
DOI: https://doi.org/10.1093/nar/gku565
Lundqvist J, Kirkegaard T, Laenkholm A-V, Duun-Henriksen AK, Bak M, Feldman D, et al. Williams syndrome transcription factor (WSTF) acts as an activator of estrogen receptor signaling in breast cancer cells and the effect can be abrogated by 1α,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol 2018;177:171-8.
DOI: https://doi.org/10.1016/j.jsbmb.2017.06.003
Liu Y, Wang S-Q, Long Y-H, Chen S, Li Y-F, Zhang J-H. KRASG12 mutant induces the release of the WSTF/NRG3 complex, and contributes to an oncogenic paracrine signaling pathway. Oncotarget 2016;7:53153-64.
DOI: https://doi.org/10.18632/oncotarget.10625
Dong C, Sun J, Ma S, Zhang G. K-ras-ERK1/2 down-regulates H2A.X(Y142ph) through WSTF to promote the progress of gastric cancer. BMC Cancer 2019;19:530.
DOI: https://doi.org/10.1186/s12885-019-5750-x
Alifieris C, Trafalis DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther 2015;152:63-82.
DOI: https://doi.org/10.1016/j.pharmthera.2015.05.005
Annovazzi L, Caldera V, Mellai M, Riganti C, Battaglia L, Chirio D, et al. The DNA damage/repair cascade in glioblastoma cell lines after chemotherapeutic agent treatment. Int J Oncol 2015;46:2299-308.
DOI: https://doi.org/10.3892/ijo.2015.2963
Yang S, Quaresma AJC, Nickerson JA, Green KM, Shaffer SA, Imbalzano AN, et al. Subnuclear domain proteins in cancer cells support the functions of RUNX2 in the DNA damage response. J Cell Sci 2015;128:728-40.
DOI: https://doi.org/10.1242/jcs.160051
Chen W-L, Turlova E, Sun CLF, Kim J-S, Huang S, Zhong X, et al. Xyloketal B suppresses glioblastoma cell proliferation and migration in vitro through inhibiting TRPM7-regulated PI3K/Akt and MEK/ERK signaling pathways. Mar Drugs 2015;13:2505-25.
DOI: https://doi.org/10.3390/md13042505
Balça-Silva J, Matias D, Carmo Ad, Sarmento-Ribeiro AB, Lopes MC, Moura-Neto V. Cellular and molecular mechanisms of glioblastoma malignancy: Implications in resistance and therapeutic strategies. Semin Cancer Biol. 2019;58:130-41.
DOI: https://doi.org/10.1016/j.semcancer.2018.09.007
16. Shahcheraghi S, Tchokonte-Nana V, Lotfi M, Lotfi M, Ghorbani A, Sadeghnia H. Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review. Curr Pharm Design. 2020;26.
DOI: https://doi.org/10.2174/1381612826666200131100630
17. Crespo Pomar S, Arcaro A. The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis. J Cancer Metastasis Treat 2016;2:80-9.
DOI: https://doi.org/10.20517/2394-4722.2015.72
Westhoff M-A, Karpel-Massler G, Brühl O, Enzenmüller S, La Ferla-Brühl K, Siegelin MD, et al. A critical evaluation of PI3K inhibition in glioblastoma and neuroblastoma therapy. Mol Cell Ther 2014;2:32.
DOI: https://doi.org/10.1186/2052-8426-2-32
Krassnig S, Wohlrab C, Golob-Schwarzl N, Raicht A, Haybaeck J. A profound basic characterization of eIFs in gliomas: Identifying eIF3I and 4H as Potential novel target candidates in glioma therapy. Cancers 2021;13:1482.
DOI: https://doi.org/10.3390/cancers13061482
Meng J, Zhang X-T, Liu X-L, Fan L, Li C, Sun Y, et al. WSTF promotes proliferation and invasion of lung cancer cells by inducing EMT via PI3K/Akt and IL-6/STAT3 signaling pathways. Cell Signal 2016;28:1673-82.
DOI: https://doi.org/10.1016/j.cellsig.2016.07.008
Oya H, Yokoyama A, Yamaoka I, Fujiki R, Yonezawa M, Youn M-Y, et al. Phosphorylation of Williams syndrome transcription factor by MAPK induces a switching between two distinct chromatin remodeling complexes. J Biol Chem 2009;284:32472-82.
DOI: https://doi.org/10.1074/jbc.M109.009738
Liu Y, Zhang Y-Y, Wang S-Q, Li M, Long Y-H, Li Y-F, et al. WSTF acetylation by MOF promotes WSTF activities and oncogenic functions. Oncogene 2020;39:5056-67.
DOI: https://doi.org/10.1038/s41388-020-1350-0
How to Cite
Yang, L., Du, C. ., Chen, H. ., & Diao, Z. . (2021). Downregulation of Williams syndrome transcription factor (WSTF) suppresses glioblastoma cell growth and invasion by inhibiting PI3K/AKT signal pathway. European Journal of Histochemistry, 65(4). https://doi.org/10.4081/ejh.2021.3255
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Yan Wang, Jie Sun, Ninghua Yao, Correlation of the AKT/mTOR signaling pathway with the clinicopathological features and prognosis of nasopharyngeal carcinoma , European Journal of Histochemistry: Vol. 65 No. 4 (2021)
- Xin Huang, Xuan Xu, Huajing Ke, Xiaolin Pan, Jiaoyu Ai, Ruyi Xie, Guilian Lan, Yang Hu, Yao Wu, microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway , European Journal of Histochemistry: Vol. 66 No. 2 (2022)
- Nan Li, Xue Fan, Lihong Liu, Yanbing Liu, Therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on ovarian functions through the PI3K/Akt cascade in mice with premature ovarian failure , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- Gong Cheng, Fengmin An, Zhilin Cao, Mingdi Zheng, Zhongyuan Zhao, Hao Wu, DPY30 promotes the growth and survival of osteosarcoma cell by regulating the PI3K/AKT signal pathway , European Journal of Histochemistry: Vol. 67 No. 1 (2023)
- Xiaoyan Chu, Jun Lou, Yun Yi, Linlin Zhong, Ouping Huang, Knockdown of ARHGAP30 inhibits ovarian cancer cell proliferation, migration, and invasiveness by suppressing the PI3K/AKT/mTOR signaling pathway , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- R. M. Ruggeri, E. Vitarelli, G. Barresi, F. Trimarchi, S. Benvenga, M. Trovato, The tyrosine kinase receptor c-met, its cognate ligand HGF and the tyrosine kinase receptor trasducers STAT3, PI3K and RHO in thyroid nodules associated with Hashimoto's thyroiditis: an immunohistochemical characterization , European Journal of Histochemistry: Vol. 54 No. 2 (2010)
- X.C. Xu, X. Abuduhadeer, W.B. Zhang, T. Li, H. Gao, Y.H. Wang, Knockdown of RAGE inhibits growth and invasion of gastric cancer cells , European Journal of Histochemistry: Vol. 57 No. 4 (2013)
- Huiwen Li, Bo Huang, miR-19a targeting CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells , European Journal of Histochemistry: Vol. 66 No. 1 (2022)
- Ying Wang, Shifa Yuan, Jing Ma, Hong Liu, Lizhen Huang, Fengzhen Zhang, Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells in vitro , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- Alimu Keremu, Pazila Aila, Aikebaier Tusun , Maimaitiaili Abulikemu, Xiaoguang Zou, Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway , European Journal of Histochemistry: Vol. 66 No. 3 (2022)
You may also start an advanced similarity search for this article.
