Epithelial-mesenchymal transition and cancer stem cells: A route to acquired cisplatin resistance through epigenetics in HNSCC

被引:12
作者
Lima de Oliveira, Julia [1 ]
More Milan, Thais [1 ]
Longo Bighetti-Trevisan, Rayana [1 ]
Fernandes, Roger Rodrigo [1 ]
Machado Leopoldino, Andreia [2 ]
Oliveira de Almeida, Luciana [1 ]
机构
[1] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Basic & Oral Biol, Ribeirao Preto, Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, Brazil
基金
巴西圣保罗研究基金会;
关键词
BMI-1; chemoresistance; epigenetic reprogramming; head and neck cancer; ZEB1; NECK-CANCER; HEAD; INHIBITION; EXPRESSION; MECHANISMS; BMI1; PLASTICITY; SURVIVAL;
D O I
10.1111/odi.14209
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Chemoresistance is associated with tumor recurrence, metastases, and short survival. Cisplatin is one of the most used chemotherapies in cancer treatment, including head and neck squamous cell carcinoma (HNSCC), and many patients develop resistance. Here, we established cell lines resistant to cisplatin to better understand epigenetics and biological differences driving the progression of HNSCC after treatment. Cisplatin resistance was established in CAL-27 and SCC-9 cell lines. Gene expression of HDAC1, HDAC2, SIRT1, MTA1, KAT2B, KAT6A, KAT6B, and BRD4 indicated the cisplatin activates the epigenetic machinery. Increases in tumor aggressiveness were detected by BMI-1 and KI-67 in more resistant cell lines. Changes in cellular shape and epithelial-mesenchymal transition (EMT) activation were also observed. HDAC1 and ZEB1 presented an opposite distribution with down-regulation of HDAC1 and up-regulation of ZEB1 in the course of chemoresistance. Up-regulation of ZEB1 and BMI-1 in patients with HNSCC is also associated with a poor response to therapy. Cancer stem cells (CSC) population increased significantly with chemoresistance. Down-regulation of HDAC1, HDAC2, and SIRT1 and accumulation of Vimentin and ZEB1 were observed in the CSC population. Our results suggest that in the route to cisplatin chemoresistance, epigenetic modifications can be associated with EMT activation and CSC accumulation which originate more aggressive tumors.
引用
收藏
页码:1991 / 2005
页数:15
相关论文
共 61 条
[1]   The Role of BMI1 as a Biomarker of Cancer Stem Cells in Head and Neck Cancer: A Review [J].
Allegra, Eugenia ;
Trapasso, Serena ;
Pisani, Davide ;
Puzzo, Lidia .
ONCOLOGY, 2014, 86 (04) :199-205
[2]   Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence [J].
Almeida, Luciana O. ;
Guimaraes, Douglas M. ;
Martins, Manoela D. ;
Martins, Marco A. T. ;
Warner, Kristy A. ;
Nor, Jacques E. ;
Castilho, Rogerio M. ;
Squarize, Cristiane H. .
STEM CELL RESEARCH, 2017, 21 :94-105
[3]   Profiling the Behavior of Distinct Populations of Head and Neck Cancer Stem Cells [J].
Almeida, Luciana O. ;
Guimaraes, Douglas M. ;
Squarize, Cristiane H. ;
Castilho, Rogerio M. .
CANCERS, 2016, 8 (01)
[4]   Survival of salivary gland cancer stem cells requires mTOR signaling [J].
Andrade, Nathalia P. ;
Warner, Kristy A. ;
Zhang, Zhaocheng ;
Pearson, Alexander T. ;
Mantesso, Andrea ;
Guimaraes, Douglas M. ;
Altemani, Albina ;
Mariano, Fernanda, V ;
Nunes, Fabio D. ;
Nor, Jacques E. .
CELL DEATH & DISEASE, 2021, 12 (01)
[5]   EMT, cancer stem cells and autophagy; The three main axes of metastasis [J].
Babaei, Ghader ;
Aziz, Shiva Gholizadeh-Ghaleh ;
Jaghi, Nasrin Zare Zavieyh .
BIOMEDICINE & PHARMACOTHERAPY, 2021, 133
[6]   Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics [J].
Bighetti-Trevisan, Rayana L. ;
Sousa, Lucas O. ;
Castilho, Rogerio M. ;
Almeida, Luciana O. .
STEM CELLS INTERNATIONAL, 2019, 2019
[7]   Inhibition of HDAC6 Protein Enhances Bortezomib-induced Apoptosis in Head and Neck Squamous Cell Carcinoma (HNSCC) by Reducing Autophagy [J].
Chang, Insoon ;
Wang, Cun-Yu .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (35) :18199-18209
[8]   Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma [J].
Chen, Demeng ;
Wu, Mansi ;
Li, Yang ;
Chang, Insoon ;
Yuan, Quan ;
Ekimyan-Salvo, Mari ;
Deng, Peng ;
Yu, Bo ;
Yu, Yongxin ;
Dong, Jiaqiang ;
Szymanski, John M. ;
Ramadoss, Sivakumar ;
Li, Jiong ;
Wang, Cun-Yu .
CELL STEM CELL, 2017, 20 (05) :621-+
[9]   Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1 [J].
Chen, Yu-Chih ;
Chang, Charn-Jung ;
Hsu, Han-Shui ;
Chen, Yi-Wei ;
Tai, Lung-Kuo ;
Tseng, Ling-Ming ;
Chiou, Guang-Yuh ;
Chang, Shih-Ching ;
Kao, Shou-Yen ;
Chiou, Shih-Hwa ;
Lo, Wen-Liang .
ORAL ONCOLOGY, 2010, 46 (03) :158-165
[10]   ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2 [J].
Cui, Yajie ;
Qin, Li ;
Tian, Defu ;
Wang, Ting ;
Fan, Lijing ;
Zhang, Peilian ;
Wang, Zhongqi .
CHEMOTHERAPY, 2018, 63 (05) :262-271