MAML1 promotes ESCC aggressiveness through upregulation of EMT marker TWIST1

被引:16
作者
Forghanifard, Mohammad Mahdi [1 ]
Azaraz, Shirin [2 ]
Khales, Sima [2 ]
Rad, Dorsa [2 ]
Abbaszadegan, Mohammad Reza [3 ]
机构
[1] Islamic Azad Univ, Damghan Branch, Dept Biol, Damghan, Iran
[2] Mashhad Univ Med Sci, Med Genet Res Ctr, Mashhad, Razavi Khorasan, Iran
[3] Mashhad Univ Med Sci, Immunol Res Ctr, Mashhad, Razavi Khorasan, Iran
基金
美国国家科学基金会;
关键词
MAML1; TWIST1; Esophageal squamous cell carcinoma; Epithelial mesenchymal transition; Upregulation; NOTCH SIGNALING PATHWAY; ESOPHAGEAL; EXPRESSION; COACTIVATOR; MASTERMIND; GENES; PLAYS;
D O I
10.1007/s11033-020-05356-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background Mastermind-like 1 (MAML1) is the main transcriptional co-activator of Notch signaling pathway. It plays essential roles in several pathways including MEF2C, p53, Nf-kB and Wnt/beta-catenin. TWIST1 is known as a regulator of epithelial mesenchymal transition (EMT), which is considered as a primary step in promotion of tumor cell metastasis. Since concomitant expression of these genes was observed in tumors, our aim in this study was to elucidate the linkage between MAML1 and TWIST1 co-overexpression in esophageal squamous cell carcinoma (ESCC). Results While MAML1 silencing significantly down-regulated TWIST1, its ectopic expression up-regulated TWIST1 expression in both mRNA and protein levels in KYSE-30 cells. Expression of mesenchymal markers was increased significantly after MAML1 and TWIST1 ectopic expression, while epithelial markers expression was significantly decreased after silencing of both genes. Concomitant protein expression of MAML1 and TWIST1 was significantly observed in ESCC patients. Enforced expression of TWIST1 had no impact on MAML1 gene expression in KYSE-30 cells. Conclusion The results clearly suggest transcriptional regulation of TWIST1 by MAML1 transcription factor in ESCC cells KYSE-30. Since TWIST1 is known as an EMT inducing marker, our results may revealed the mastermind behind TWIST1 function and introduced MAML1 as an upstream master regulator of TWIST1 and EMT in KYSE-30 cells.
引用
收藏
页码:2659 / 2668
页数:10
相关论文
共 38 条
[1]   Mastermind-like 1 is a specific coactivator of β-catenin transcription activation and is essential for colon carcinoma cell survival [J].
Alves-Guerra, Marie-Clotilde ;
Ronchini, Chiara ;
Capobianco, Anthony J. .
CANCER RESEARCH, 2007, 67 (18) :8690-8698
[2]   MAML1 and TWIST1 co-overexpression promote invasion of head and neck squamous cell carcinoma [J].
Ardalan Khales, Sima ;
Ebrahimi, Ehsan ;
Jahanzad, Eisa ;
Ardalan Khales, Sahar ;
Forghanifard, Mohammad Mahdi .
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, 2018, 14 (05) :e434-e441
[3]   Notch signaling: Cell fate control and signal integration in development [J].
Artavanis-Tsakonas, S ;
Rand, MD ;
Lake, RJ .
SCIENCE, 1999, 284 (5415) :770-776
[4]   A twist code determines the onset of osteoblast differentiation [J].
Bialek, P ;
Kern, B ;
Yang, XL ;
Schrock, M ;
Sosic, D ;
Hong, N ;
Wu, H ;
Yu, K ;
Ornitz, DM ;
Olson, EN ;
Justice, MJ ;
Karsenty, G .
DEVELOPMENTAL CELL, 2004, 6 (03) :423-435
[5]   Contribution of MAML1 in esophageal squamous cell carcinoma tumorigenesis [J].
Bidokhti, Mahnaz Hashemi ;
Abbaszadegan, Mohammad Reza ;
Sharifi, Noorieh ;
Sani, Soodabeh Abbasi ;
Forghanifard, Mohammad Mandi .
ANNALS OF DIAGNOSTIC PATHOLOGY, 2017, 27 :79-82
[6]   Insulin-like growth factor 1 (IGF-1)-induced Twist expression is involved in the anti-apoptotic effects of the IGF-1 receptor [J].
Dupont, J ;
Fernandez, AM ;
Glackin, CA ;
Helman, L ;
LeRoith, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (28) :26699-26707
[7]   Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells [J].
Espinoza, Ingrid ;
Miele, Lucio .
CANCER LETTERS, 2013, 341 (01) :41-45
[8]   TWIST1 upregulates the MAGEA4 oncogene [J].
Forghanifard, Mohammad Mahdi ;
Rad, Abolfazl ;
Farshchian, Moein ;
Khaleghizadeh, Maryam ;
Gholamin, Mehran ;
Moghbeli, Meysam ;
Abbaszadegan, Mohammad Reza .
MOLECULAR CARCINOGENESIS, 2017, 56 (03) :877-885
[9]   Notch Signaling Target Genes are Directly Correlated to Esophageal Squamous Cell Carcinoma Tumorigenesis [J].
Forghanifard, Mohammad Mahdi ;
Taleb, Shaghayegh ;
Abbaszadegan, Mohammad Reza .
PATHOLOGY & ONCOLOGY RESEARCH, 2015, 21 (02) :463-467
[10]   Neoantigen in esophageal squamous cell carcinoma for dendritic cell-based cancer vaccine development [J].
Forghanifard, Mohammad Mahdi ;
Gholamin, Mehran ;
Moaven, Omeed ;
Farshchian, Moein ;
Ghahraman, Martha ;
Aledavood, Amir ;
Abbaszadegan, Mohammad Reza .
MEDICAL ONCOLOGY, 2014, 31 (10)