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Published in: Annals of Surgical Oncology 3/2012

01-03-2012 | Thoracic Oncology

Expression Analysis Elucidates the Roles of MAML1 and Twist1 in Esophageal Squamous Cell Carcinoma Aggressiveness and Metastasis

Authors: Mohammad Mahdi Forghanifard, PhD, Omeed Moaven, MD, Moein Farshchian, MSc, Mehdi Montazer, MD, Reza Raeisossadati, MSc, Abbas Abdollahi, MD, Meysam Moghbeli, MSc, Taher Nejadsattari, PhD, Kazem Parivar, PhD, Mohammad Reza Abbaszadegan, PhD

Published in: Annals of Surgical Oncology | Issue 3/2012

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Abstract

Background

Epithelial-mesenchymal transition has recently attracted great attention in studying the malignant progression of cells through a converging pathway of oncogenesis and metastasis. Twist1 and Mastermind-like 1 (MAML1) are major regulators of EMT through different pathways. The aim of this study was to investigate the clinicopathological relevance of the expression of MAML-1 and Twist1 genes in esophageal squamous cell carcinoma (ESCC).

Methods

Tumoral and corresponding normal tissues from 55 treatment-naive ESCC patients were subjected for expression analysis with quantitative real-time RT-PCR.

Results

Overexpression of MAML-1 and Twist1 were significantly associated with lymph node metastasis and the surgical staging of tumor. Overexpression of Twist1 was associated with tumor depth of invasion. Mean relative expression (MRE) of MAML1 was significantly higher in patients with metastasis to lymph nodes (3.07 ± 0.51 vs. 0.86 ± 0.58, P = .008). MRE of Twist1 was significantly higher in patients with invasion of tumor to adventitia (T3, T4) (1.97 ± 0.29 vs. 0.39 ± 0.73, P = .036). In advanced stages of tumor (stage III, IV), a significantly higher MRE of Twist1 (2.47 ± 0.41 vs. 1.25 ± 0.36, P = .035) and MAML1 (3.05 ± 0.45 vs. 1.07 ± 0.59, P = .021) mRNA was observed.

Conclusions

We introduce Twist1 and MAML1 as new molecular markers of advanced tumor, which determine the characteristics and aggressive behavior of ESCC. Along with the emerging evidence of their role in different cellular processes and aberrations in various cancers, they are suggested as potentially interesting therapeutic targets to reverse a broad spectrum of functional aberrations that promote ESCC development.
Literature
1.
go back to reference Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, et al. Significance of Twist expression and its association with E-cadherin in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2009;28:158.PubMedCrossRef Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, et al. Significance of Twist expression and its association with E-cadherin in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2009;28:158.PubMedCrossRef
2.
go back to reference Ansieau S, Morel AP, Hinkal G, Bastid J, Puisieux A. TWISTing an embryonic transcription factor into an oncoprotein. Oncogene. 2010;29:3173–84.PubMedCrossRef Ansieau S, Morel AP, Hinkal G, Bastid J, Puisieux A. TWISTing an embryonic transcription factor into an oncoprotein. Oncogene. 2010;29:3173–84.PubMedCrossRef
3.
go back to reference Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66:8319–26.PubMedCrossRef Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66:8319–26.PubMedCrossRef
4.
go back to reference Klymkowsky MW, Savagner P. Epithelial-mesenchymal transition: a cancer researcher’s conceptual friend and foe. Am J Pathol. 2009;174:1588–93.PubMedCrossRef Klymkowsky MW, Savagner P. Epithelial-mesenchymal transition: a cancer researcher’s conceptual friend and foe. Am J Pathol. 2009;174:1588–93.PubMedCrossRef
5.
go back to reference Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.PubMedCrossRef Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.PubMedCrossRef
6.
go back to reference Yuen HF, Chan YP, Wong ML, Kwok WK, Chan KK, Lee PY, et al. Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol. 2007;60:510–4.PubMedCrossRef Yuen HF, Chan YP, Wong ML, Kwok WK, Chan KK, Lee PY, et al. Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol. 2007;60:510–4.PubMedCrossRef
7.
go back to reference Katoh M, Katoh M. Notch signaling in gastrointestinal tract (review). Int J Oncol. 2007;30:247–51.PubMed Katoh M, Katoh M. Notch signaling in gastrointestinal tract (review). Int J Oncol. 2007;30:247–51.PubMed
8.
go back to reference Wu L, Griffin JD. Modulation of Notch signaling by mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis. Semin Cancer Biol. 2004;14:348–56.PubMedCrossRef Wu L, Griffin JD. Modulation of Notch signaling by mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis. Semin Cancer Biol. 2004;14:348–56.PubMedCrossRef
10.
go back to reference Watt FM, Estrach S, Ambler CA. Epidermal Notch signalling: differentiation, cancer and adhesion. Curr Opin Cell Biol. 2008;20:171–9.PubMedCrossRef Watt FM, Estrach S, Ambler CA. Epidermal Notch signalling: differentiation, cancer and adhesion. Curr Opin Cell Biol. 2008;20:171–9.PubMedCrossRef
11.
go back to reference McElhinny AS, Li JL, Wu L. Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways. Oncogene. 2008;27:5138–47.PubMedCrossRef McElhinny AS, Li JL, Wu L. Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways. Oncogene. 2008;27:5138–47.PubMedCrossRef
12.
13.
go back to reference Proweller A, Tu L, Lepore JJ, Cheng L, Lu MM, Seykora J, et al. Impaired notch signaling promotes de novo squamous cell carcinoma formation. Cancer Res. 2006;66:7438–44.PubMedCrossRef Proweller A, Tu L, Lepore JJ, Cheng L, Lu MM, Seykora J, et al. Impaired notch signaling promotes de novo squamous cell carcinoma formation. Cancer Res. 2006;66:7438–44.PubMedCrossRef
14.
go back to reference Wu L, Sun T, Kobayashi K, Gao P, Griffin JD. Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors. Mol Cell Biol. 2002;22:7688–700.PubMedCrossRef Wu L, Sun T, Kobayashi K, Gao P, Griffin JD. Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors. Mol Cell Biol. 2002;22:7688–700.PubMedCrossRef
15.
go back to reference Sobin LH. TNM Classification of Malignant Tumours. 7th edition, Chichester, U.K., Wiley-Blackwell, 2009. Sobin LH. TNM Classification of Malignant Tumours. 7th edition, Chichester, U.K., Wiley-Blackwell, 2009.
16.
go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCrossRef Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCrossRef
17.
go back to reference Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet. 2000;26:484–9.PubMedCrossRef Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet. 2000;26:484–9.PubMedCrossRef
18.
go back to reference Chen J, Imanaka N, Chen J, Griffin JD. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer. 2009;102:351–60.PubMedCrossRef Chen J, Imanaka N, Chen J, Griffin JD. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer. 2009;102:351–60.PubMedCrossRef
19.
go back to reference Taghavi N, Biramijamal F, Sotoudeh, M, Khademi H, Malekzadeh R, Moaven O, et al. p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in esophageal squamous cell carcinoma. BMC Cancer. 2010;10:138.PubMedCrossRef Taghavi N, Biramijamal F, Sotoudeh, M, Khademi H, Malekzadeh R, Moaven O, et al. p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in esophageal squamous cell carcinoma. BMC Cancer. 2010;10:138.PubMedCrossRef
20.
go back to reference Ayyanan A, Civenni G, Ciarloni L, Morel C, Mueller N, Lefort K, et al. Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. Proc Natl Acad Sci U S A. 2006;103:3799–804.PubMedCrossRef Ayyanan A, Civenni G, Ciarloni L, Morel C, Mueller N, Lefort K, et al. Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. Proc Natl Acad Sci U S A. 2006;103:3799–804.PubMedCrossRef
21.
go back to reference Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, et al. Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 2009;15:2657–65.PubMedCrossRef Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, et al. Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 2009;15:2657–65.PubMedCrossRef
22.
go back to reference Vincent-Salomon A, Thiery JP. Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development. Breast Cancer Res. 2003;5:101–6.PubMedCrossRef Vincent-Salomon A, Thiery JP. Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development. Breast Cancer Res. 2003;5:101–6.PubMedCrossRef
23.
go back to reference Tsuji T, Ibaragi S, Hu GF. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res. 2009;69:7135–9.PubMedCrossRef Tsuji T, Ibaragi S, Hu GF. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res. 2009;69:7135–9.PubMedCrossRef
24.
go back to reference Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12:488–96.PubMedCrossRef Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12:488–96.PubMedCrossRef
25.
go back to reference Luo GQ, Li JH, Wen JF, Zhou YH, Hu YB, Zhou JH. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells. World J Gastroenterol. 2008;14:2487–93.PubMedCrossRef Luo GQ, Li JH, Wen JF, Zhou YH, Hu YB, Zhou JH. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells. World J Gastroenterol. 2008;14:2487–93.PubMedCrossRef
26.
go back to reference Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I, et al. Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 2007;204:2935–48.PubMedCrossRef Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I, et al. Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 2007;204:2935–48.PubMedCrossRef
27.
go back to reference Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119:1420–8.PubMedCrossRef Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119:1420–8.PubMedCrossRef
28.
go back to reference Yang Z, Zhang X, Gang H, Li X, Li Z, Wang T, et al. Up-regulation of gastric cancer cell invasion by Twist is accompanied by N-cadherin and fibronectin expression. Biochem Biophys Res Commun. 2007;358:925–30.PubMedCrossRef Yang Z, Zhang X, Gang H, Li X, Li Z, Wang T, et al. Up-regulation of gastric cancer cell invasion by Twist is accompanied by N-cadherin and fibronectin expression. Biochem Biophys Res Commun. 2007;358:925–30.PubMedCrossRef
29.
go back to reference Kogan-Sakin I, Tabach Y, Buganim Y, Molchadsky A, Solomon H, Madar S, et al. Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial-mesenchymal transition in immortalized prostate cells. Cell Death Differ. 2011;18:271–81.PubMedCrossRef Kogan-Sakin I, Tabach Y, Buganim Y, Molchadsky A, Solomon H, Madar S, et al. Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial-mesenchymal transition in immortalized prostate cells. Cell Death Differ. 2011;18:271–81.PubMedCrossRef
30.
go back to reference Yang MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, et al. Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol. 2010;12:982–92.PubMedCrossRef Yang MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, et al. Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol. 2010;12:982–92.PubMedCrossRef
31.
go back to reference Wang X, Ling MT, Guan XY, Tsao SW, Cheung HW, Lee DT, et al. Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene. 2004;23:474–82.PubMedCrossRef Wang X, Ling MT, Guan XY, Tsao SW, Cheung HW, Lee DT, et al. Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene. 2004;23:474–82.PubMedCrossRef
32.
go back to reference Shiota M, Yokomizo A, Itsumi M, Uchiumi T, Tada Y, Song Y, et al. Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells. BJU Int. 2011;108:E142–9.PubMedCrossRef Shiota M, Yokomizo A, Itsumi M, Uchiumi T, Tada Y, Song Y, et al. Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer cells. BJU Int. 2011;108:E142–9.PubMedCrossRef
33.
Metadata
Title
Expression Analysis Elucidates the Roles of MAML1 and Twist1 in Esophageal Squamous Cell Carcinoma Aggressiveness and Metastasis
Authors
Mohammad Mahdi Forghanifard, PhD
Omeed Moaven, MD
Moein Farshchian, MSc
Mehdi Montazer, MD
Reza Raeisossadati, MSc
Abbas Abdollahi, MD
Meysam Moghbeli, MSc
Taher Nejadsattari, PhD
Kazem Parivar, PhD
Mohammad Reza Abbaszadegan, PhD
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2074-8

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