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Original Articles
- RASSF1A Suppresses Cell Migration through Inactivation of HDAC6 and Increase of Acetylated alpha-Tubulin
- Hae-Yun Jung, Jun Seok Jung, Young Mi Whang, Yeul Hong Kim
- Cancer Res Treat. 2013;45(2):134-144. Published online June 30, 2013
- DOI: https://doi.org/10.4143/crt.2013.45.2.134
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Abstract
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ePub - PURPOSE
The RAS association domain family protein 1 (RASSF1) has been implicated in a tumor-suppressive function through the induction of acetylated alpha-tubulin and modulation of cell migration. However, the mechanisms of how RASSF1A is associated with acetylation of alpha-tubulin for controlling cell migration have not yet been elucidated. In this study, we found that RASSF1A regulated cell migration through the regulation of histon deacetylase 6 (HDAC6), which functions as a tubulin deacetylase.
MATERIALS AND METHODS
The cell migration was assessed using wound-healing and transwell assays. The role of RASSF1A on cell migration was examined by immunofluorescence staining, HDAC activity assay and western blot analysis.
RESULTS
Cell migration was inhibited and cell morphology was changed in RASSF1A-transfected H1299 cells, compared with controls, whereas HDAC6 protein expression was not changed by RASSF1A transfection in these cells. However, RASSF1A inhibited deacetylating activity of HDAC6 protein and induced acetylated alpha-tubulin expression. Furthermore, acetylated alpha-tubulin and HDAC6 protein were co-localized in the cytoplasm in RASSF1A-transfected H1299 cells. Conversely, when the endogenous RASSF1A expression in HeLa cells was blocked with RASSF1A siRNA treatment, acetylated alpha-tubulin was co-localized with HDAC6 protein throughout the whole cells, including the nucleus, compared with scramble siRNA-treated HeLa cells. The restoration of RASSF1A by 5-Aza-dC treatment also induced acetylated alpha-tubulin through inhibition of HDAC6 activity that finally resulted in suppressing cell migration in H1299 cells. To further confirm the role of HDAC6 in RASSF1A-mediated cell migration, the HDAC6 expression in H1299 cells was suppressed by using HDAC6 siRNA, and cell motility was found to be decreased through enhanced acetylated alpha-tubulin.
CONCLUSION
The results of this study suggest that the inactivation of HDAC6 by RASSF1A regulates cell migration through increased acetylated alpha-tubulin protein. -
Citations
Citations to this article as recorded by
- Paxillin/HDAC6 regulates microtubule acetylation to promote directional migration of keratinocytes driven by electric fields
Luojia Liu, Xiaoqiang Liu, Ying Chen, Meng Kong, Jinghong Zhang, Min Jiang, Hongling Zhou, Jinrui Yang, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jiaping Zhang
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2024; 1871(2): 119628. CrossRef - Inhibition of histone deacetylase 6 destabilizes ERK phosphorylation and suppresses cancer proliferation via modulation of the tubulin acetylation-GRP78 interaction
Onsurang Wattanathamsan, Naphat Chantaravisoot, Piriya Wongkongkathep, Sakkarin Kungsukool, Paninee Chetprayoon, Pithi Chanvorachote, Chanida Vinayanuwattikun, Varisa Pongrakhananon
Journal of Biomedical Science.2023;[Epub] CrossRef - Inter-relationship of Histone Deacetylase-6 with Tau-cytoskeletal organization and remodeling
Abhishek Ankur Balmik, Subashchandrabose Chinnathambi
European Journal of Cell Biology.2022; 101(2): 151202. CrossRef - HDAC6 inhibitor, ACY1215 suppress the proliferation and induce apoptosis of gallbladder cancer cells and increased the chemotherapy effect of gemcitabine and oxaliplatin
Yi Ruan, Luoluo Wang, Yeting Lu
Drug Development Research.2021; 82(4): 598. CrossRef - Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/α-tubulin acetylation
Changhan Ouyang, Jing Mu, Qiulun Lu, Jian Li, Huaiping Zhu, Qilong Wang, Ming-Hui Zou, Zhonglin Xie
Autophagy.2020; 16(10): 1753. CrossRef - RASSF1A Regulates Spindle Organization by Modulating Tubulin Acetylation via SIRT2 and HDAC6 in Mouse Oocytes
Hyuk-Joon Jeon, Jeong Su Oh
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef - The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries
Zsofia Kutil, Lubica Skultetyova, David Rauh, Marat Meleshin, Ivan Snajdr, Zora Novakova, Jana Mikesova, Jiri Pavlicek, Martin Hadzima, Petra Baranova, Barbora Havlinova, Pavel Majer, Mike Schutkowski, Cyril Barinka
The FASEB Journal.2019; 33(3): 4035. CrossRef - Suppressor of hepatocellular carcinoma RASSF1A activates autophagy initiation and maturation
Wenjiao Li, Fei Yue, Yuan Dai, Boyun Shi, Guibin Xu, Xianhan Jiang, Xinke Zhou, Gerd P. Pfeifer, Leyuan Liu
Cell Death & Differentiation.2019; 26(8): 1379. CrossRef - The Role and Function of Ras-association domain family in Cancer: A Review
Mohammad Reza Zinatizadeh, Seyed Ali Momeni, Peyman Kheirandish Zarandi, Ghanbar Mahmoodi Chalbatani, Hassan Dana, Hamid Reza Mirzaei, Mohammad Esmaeil Akbari, Seyed Rouhollah Miri
Genes & Diseases.2019; 6(4): 378. CrossRef - RASSF1A, puppeteer of cellular homeostasis, fights tumorigenesis, and metastasis—an updated review
Fatéméh Dubois, Emmanuel Bergot, Gérard Zalcman, Guénaëlle Levallet
Cell Death & Disease.2019;[Epub] CrossRef - Tumor suppressor C-RASSF proteins
Hiroaki Iwasa, Shakhawoat Hossain, Yutaka Hata
Cellular and Molecular Life Sciences.2018; 75(10): 1773. CrossRef - Dual-functionality of RASSF1A overexpression in A375 cells is mediated by activation of IL-6/STAT3 regulatory loop
Mei Yi, Wei Wang, Shengnan Chen, Ya Peng, Junjun Li, Jing Cai, Ying Zhou, Qian Peng, Yuanyuan Ban, Zhaoyang Zeng, Xiaoling Li, Wei Xiong, Guiyuan Li, Bo Xiang
Molecular Biology Reports.2018; 45(5): 1277. CrossRef - Epigenetic reactivation of RASSF1A by phenethyl isothiocyanate (PEITC) and promotion of apoptosis in LNCaP cells
Sarandeep S.S. Boyanapalli, Wenji Li, Francisco Fuentes, Yue Guo, Christina N. Ramirez, Ximena-Parades Gonzalez, Douglas Pung, Ah-Ng Tony Kong
Pharmacological Research.2016; 114: 175. CrossRef - The Potential of Histone Deacetylase Inhibitors in Breast Cancer Therapy
Namita Chatterjee, Martin Tenniswood
Breast Cancer Management.2015; 4(2): 85. CrossRef - CpG site-specific RASSF1a hypermethylation is associated with occupational PAH exposure and genomic instability
Zhini He, Huawei Duan, Biao Zhang, Miao Li, Liping Chen, Bo Zhang, Xiaonian Zhu, Chen Gao, Jie Li, Xiao Zhang, Jingmaio Zhang, Shan Wang, Xiaowen Zeng, Daochuan Li, Xiumei Xing, Zhengbao Zhang, Lu Ma, Qing Bai, Caixia Liu, Yongmei Xiao, Yuxin Zheng, Wen C
Toxicology Research.2015; 4(4): 848. CrossRef - Microtubule segment stabilization by RASSF1A is required for proper microtubule dynamics and Golgi integrity
Christopher Arnette, Nadia Efimova, Xiaodong Zhu, Geoffrey J. Clark, Irina Kaverina, Erika Holzbaur
Molecular Biology of the Cell.2014; 25(6): 800. CrossRef - RASSF tumor suppressor gene family: Biological functions and regulation
Natalia Volodko, Marilyn Gordon, Mohamed Salla, Haya Abu Ghazaleh, Shairaz Baksh
FEBS Letters.2014; 588(16): 2671. CrossRef - MicroRNA expression profiling in male and female familial breast cancer
R Pinto, S De Summa, K Danza, O Popescu, A Paradiso, L Micale, G Merla, O Palumbo, M Carella, S Tommasi
British Journal of Cancer.2014; 111(12): 2361. CrossRef
- Paxillin/HDAC6 regulates microtubule acetylation to promote directional migration of keratinocytes driven by electric fields
- 12,949 View
- 138 Download
- 18 Crossref
- The Blocking of c-Met Signaling Induces Apoptosis through the Increase of p53 Protein in Lung Cancer
- Hae-Yun Jung, Hyun-Jung Joo, Jong Kuk Park, Yeul Hong Kim
- Cancer Res Treat. 2012;44(4):251-261. Published online December 31, 2012
- DOI: https://doi.org/10.4143/crt.2012.44.4.251
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Abstract
PDFPubReaderePub
- PURPOSE
c-Met is an attractive potential target for novel therapeutic inhibition of human cancer, and c-Met tyrosine kinase inhibitors (TKIs) are effective growth inhibitors of various malignancies. However, their mechanisms in anticancer effects are not clear. In the present study, we investigated the possibility that blocking c-Met signaling induces p53-mediated growth inhibition in lung cancer.
MATERIALS AND METHODS
The growth inhibitory effects of c-Met TKI (SU11274) on lung cancer cells and a xenograft model were assessed using the MTT assay, flow cytometry, and terminal deoxyribonucleotide transferase-mediated nick-end labeling staining. The role of p53 protein in the sensitivity of c-Met TKI (SU11274) was examined by Western blot analysis and immunohistochemistry.
RESULTS
SU11274 significantly induced apoptosis in A549 cells with wild-type p53, compared with that in Calu-1 cells with null-type p53. SU11274 increased p53 protein by enhancing the stability of p53 protein. Increased p53 protein by SU11274 induced up-regulation of Bax and PUMA expression and down-regulation of Bcl-2 expression, subsequently activating caspase 3. In p53 knock-out and knock-in systems, we confirmed that SU11274 caused apoptosis through the p53-mediated apoptotic pathway. Likewise, in the A549 xenograft model, SU11274 effectively shrank tumor volume and induced apoptosis via increased p53 protein expression. Blocking c-Met signaling increased the level of p53 protein.
CONCLUSION
Our finding suggested that p53 plays an important role in SU11274-induced apoptosis, and p53 status seems to be related to the sensitivity to SU11274 in lung cancer. -
Citations
Citations to this article as recorded by- Fragment-based design and synthesis of coumarin-based thiazoles as dual c-MET/STAT-3 inhibitors for potential antitumor agents
Bassem H. Naguib, Heba A. Elsebaie, Mohamed S. Nafie, Samy Mohamady, Nader R. Albujuq, Aya Samir Ayed, Dina Nada, Ahmed F. Khalil, Salma M. Hefny, Haytham O. Tawfik, Moataz A. Shaldam
Bioorganic Chemistry.2024; 151: 107682. CrossRef - A Boolean Model of the Proliferative Role of the lncRNA XIST in Non-Small Cell Lung Cancer Cells
Shantanu Gupta, Daner A. Silveira, Ronaldo F. Hashimoto, Jose Carlos M. Mombach
Biology.2022; 11(4): 480. CrossRef - Artonin F Induces the Ubiquitin-Proteasomal Degradation of c-Met and Decreases Akt-mTOR Signaling
Rapeepun Soonnarong, Ismail Dwi Putra, Nicharat Sriratanasak, Boonchoo Sritularak, Pithi Chanvorachote
Pharmaceuticals.2022; 15(5): 633. CrossRef - Targeted inhibition of c-MET by podophyllotoxin promotes caspase-dependent apoptosis and suppresses cell growth in gefitinib-resistant non-small cell lung cancer cells
Ha-Na Oh, Ah-Won Kwak, Mee-Hyun Lee, Eunae Kim, Goo Yoon, Seung-Sik Cho, Kangdong Liu, Jung-Il Chae, Jung-Hyun Shim
Phytomedicine.2021; 80: 153355. CrossRef - Identification of four methylation-driven genes as candidate biomarkers for monitoring single-walled carbon nanotube-induced malignant transformation of the lung
Dongli Xie, Xiaogang Luo
Toxicology and Applied Pharmacology.2021; 412: 115391. CrossRef - Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer
Fatemeh Moosavi, Elisa Giovannetti, Godefridus J. Peters, Omidreza Firuzi
Critical Reviews in Oncology/Hematology.2021; 160: 103234. CrossRef - Pharmacological inhibition of the MEK5/ERK5 and PI3K/Akt signaling pathways synergistically reduces viability in triple‐negative breast cancer
Thomas D. Wright, Christopher Raybuck, Akshita Bhatt, Darlene Monlish, Suravi Chakrabarty, Katy Wendekier, Nathan Gartland, Mohit Gupta, Matthew E. Burow, Patrick T. Flaherty, Jane E. Cavanaugh
Journal of Cellular Biochemistry.2020; 121(2): 1156. CrossRef - The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells
Ibraheem M. Attafi, Saleh A. Bakheet, Hesham M. Korashy
Toxicology Mechanisms and Methods.2020; 30(3): 197. CrossRef - Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action
Khaled AbouAitah, Anna Swiderska-Sroda, Ahmed A. Farghali, Jacek Wojnarowicz, Agata Stefanek, Stanislaw Gierlotka, Agnieszka Opalinska, Abdou K. Allayeh, Tomasz Ciach, Witold Lojkowski
Oncotarget.2018; 9(41): 26466. CrossRef - Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression
Yang Chen, Qin Zhang, Qiuyan Wang, Jie Li, Csilla Sipeky, Jihan Xia, Ping Gao, Yanling Hu, Haiying Zhang, Xiaobo Yang, Haitao Chen, Yonghua Jiang, Yuehong Yang, Ziting Yao, Yinchun Chen, Yong Gao, Aihua Tan, Ming Liao, Johanna Schleutker, Jianfeng Xu, Yin
Scientific Reports.2017;[Epub] CrossRef - Regulation of theMEToncogene: molecular mechanisms
Jack Zhang, Andy Babic
Carcinogenesis.2016; 37(4): 345. CrossRef - The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: A pooled analysis of 41 sets of data from case–control studies
Yang Chen, Tianyu Li, Xiaoqiang Yu, Jianfeng Xu, Jianling Li, Dexiang Luo, Zengnan Mo, Yanling Hu
Gene.2014; 534(2): 286. CrossRef - miR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation
JianFeng Xu, ZheYong Huang, Li Lin, MingQiang Fu, YanHua Gao, YunLi Shen, YunZeng Zou, AiJun Sun, JuYing Qian, JunBo Ge
Science China Life Sciences.2014; 57(10): 989. CrossRef - Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2
Mario Acunzo, Giulia Romano, Dario Palmieri, Alessandro Laganá, Michela Garofalo, Veronica Balatti, Alessandra Drusco, Mario Chiariello, Patrick Nana-Sinkam, Carlo M. Croce
Proceedings of the National Academy of Sciences.2013; 110(21): 8573. CrossRef - Gold nanoparticles trigger apoptosis and necrosis in lung cancer cells with low intracellular glutathione
Min Liu, Xiaohu Gu, Ke Zhang, Yi Ding, Xinbing Wei, Xiumei Zhang, Yunxue Zhao
Journal of Nanoparticle Research.2013;[Epub] CrossRef - RTK/ERK Pathway under Natural Selection Associated with Prostate Cancer
Yang Chen, Xianxiang Xin, Jie Li, Jianfeng Xu, Xiaoxiang Yu, Tianyu Li, Zengnan Mo, Yanling Hu, Antimo Migliaccio
PLoS ONE.2013; 8(11): e78254. CrossRef
- Fragment-based design and synthesis of coumarin-based thiazoles as dual c-MET/STAT-3 inhibitors for potential antitumor agents
- 13,137 View
- 71 Download
- 16 Crossref
- An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population
- Wonbeak Yoo, Hae-Yun Jung, Seungjoon Lim, Jae Sook Sung, Kyong Hwa Park, Jeong Seon Ryu, Sang Won Shin, Jun Suk Kim, Jae Hong Seo, Yeul Hong Kim
- Cancer Res Treat. 2011;43(2):108-116. Published online June 30, 2011
- DOI: https://doi.org/10.4143/crt.2011.43.2.108
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Abstract
PDFPubReaderePub
- PURPOSE
The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population.
MATERIALS AND METHODS
A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk.
RESULTS
Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer.
CONCLUSION
JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population. -
Citations
Citations to this article as recorded by- Association Analysis of Polymorphic Gene Variants in the JAK/STAT Signaling Pathway with Aging and Longevity
V. V. Erdman, T. R. Nasibullin, I. A. Tuktarova, R. Sh. Somova, O. E. Mustafina
Russian Journal of Genetics.2019; 55(6): 728. CrossRef
- Association Analysis of Polymorphic Gene Variants in the JAK/STAT Signaling Pathway with Aging and Longevity
- 10,766 View
- 55 Download
- 1 Crossref
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