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Erschienen in: Pathology & Oncology Research 2/2016

01.04.2016 | Original Article

Contribution of EVX1 in Aggressiveness of Esophageal Squamous Cell Carcinoma

verfasst von: Afsaneh Javdani Mallak, Mohammad Reza Abbaszadegan, Pegah Naeemi Khorasanizadeh, Mohammad Mahdi Forghanifard

Erschienen in: Pathology & Oncology Research | Ausgabe 2/2016

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Abstract

Homeobox genes play an overruling role in the regional cell fate determination during development. EVX1 is known as a new target gene of BMP signaling pathway, a group of morphogens which are making the largest subset within the transformation growth factor beta (TGF-β) superfamily. In this study, we aimed to enlighten the expression level of EVX1 in esophageal squamous cell carcinoma (ESCC) and to disclose its apparent roles in maintenance and progression of the disease. The expression level of EVX1 was analyzed in fresh tumoral tissues in comparison with distant tumor-free tissues of 50 ESCC patients using relative comparative real-time PCR. The importance of EVX1 in development and cancer was also reviewed. EVX1 was underexpressed in 70 % of tumor samples. There was a significant correlation between down-regulation of EVX1 and lymph node metastasis of tumor cells (p = 0.027). Furthermore, EVX1 underexpression was significantly correlated with depth of tumor cell invasion (P = 0.037). To the best of our knowledge, this is the first report highlighting EVX1 expression in ESCC to date. The clinicopathological relevance of EVX1 mRNA expression in ESCC targeted this gene as a new independent molecular marker for advanced tumor, which determine the characteristics and behavior of aggressive ESCC.
Literatur
1.
Zurück zum Zitat Ruiz i Altaba A, Choi T, Melton DA (1991) Expression of the Xhox3 homeobox protein in xenopus embryos: blocking its early function suggests the requirement of Xhox3 for normal posterior development. Develop Growth Differ 33:651–669CrossRef Ruiz i Altaba A, Choi T, Melton DA (1991) Expression of the Xhox3 homeobox protein in xenopus embryos: blocking its early function suggests the requirement of Xhox3 for normal posterior development. Develop Growth Differ 33:651–669CrossRef
2.
Zurück zum Zitat Ruiz i Altaba A, Melton DA (1989a) Bimodal and graded expression of the xenopus homeobox gene Xhox3 during embryonic development. Development 106:173–183PubMed Ruiz i Altaba A, Melton DA (1989a) Bimodal and graded expression of the xenopus homeobox gene Xhox3 during embryonic development. Development 106:173–183PubMed
3.
Zurück zum Zitat Ruiz i Altaba A, Melton DA (1989b) Involvement of the xenopus homeobox gene Xhox3 in pattern formation along the anterior–posterior axis. Cell 57:317–326CrossRefPubMed Ruiz i Altaba A, Melton DA (1989b) Involvement of the xenopus homeobox gene Xhox3 in pattern formation along the anterior–posterior axis. Cell 57:317–326CrossRefPubMed
4.
Zurück zum Zitat Briata P, Van De Werken R, Airoldi I, Ilengo C, Di Blas E, Boncinelli E, Corte G (1995) Transcriptional repression by the human homeobox protein EVX1 in transfected mammalian cells. J Biophys Chem 270:27695–27701. doi:10.1074/jbc.270.46.27695 Briata P, Van De Werken R, Airoldi I, Ilengo C, Di Blas E, Boncinelli E, Corte G (1995) Transcriptional repression by the human homeobox protein EVX1 in transfected mammalian cells. J Biophys Chem 270:27695–27701. doi:10.​1074/​jbc.​270.​46.​27695
5.
Zurück zum Zitat Hui X, Long-jiang L, Fang X, Bo H, Zhuang Z, Jiang W (2012) Differentially expressed homeobox genes in salivary adenoid cystic carcinoma versus normal salivary gland tissue. Life Sci J 9(2):292–296 Hui X, Long-jiang L, Fang X, Bo H, Zhuang Z, Jiang W (2012) Differentially expressed homeobox genes in salivary adenoid cystic carcinoma versus normal salivary gland tissue. Life Sci J 9(2):292–296
12.
13.
Zurück zum Zitat Zhai Y, Kuick R, Nan B, Ota I, Weiss SJ, Trimble CL, Fearon ER, Cho KR (2007) Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC10 as a key mediator of invasion. Cancer Res 67(21):10163–10172. doi:10.1158/0008-5472.CAN-07-2056 CrossRefPubMed Zhai Y, Kuick R, Nan B, Ota I, Weiss SJ, Trimble CL, Fearon ER, Cho KR (2007) Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC10 as a key mediator of invasion. Cancer Res 67(21):10163–10172. doi:10.​1158/​0008-5472.​CAN-07-2056 CrossRefPubMed
14.
Zurück zum Zitat Sobin LH, Gospodarowicz MK, Wittekind C (2011) TNM classification of malignant tumours. Wiley, London Sobin LH, Gospodarowicz MK, Wittekind C (2011) TNM classification of malignant tumours. Wiley, London
16.
Zurück zum Zitat Rauch T, Wang Z, Zhang X, Zhong X, Wu X, Lau SK, Kernstine KH, Riggs AD, Pfeifer GP (2007) Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay. Proc Natl Acad Sci U S A 104(13):5527–5532. doi:10.1073/pnas.0701059104 CrossRefPubMedPubMedCentral Rauch T, Wang Z, Zhang X, Zhong X, Wu X, Lau SK, Kernstine KH, Riggs AD, Pfeifer GP (2007) Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay. Proc Natl Acad Sci U S A 104(13):5527–5532. doi:10.​1073/​pnas.​0701059104 CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Osada S, Ohmori SY, Taira M (2003) XMAN1, an inner nuclear membrane protein, antagonizes BMP signaling by interacting with Smad1 in xenopus embryos. Development 130(9):1783–1794. doi:10.1242/dev.00401 CrossRefPubMed Osada S, Ohmori SY, Taira M (2003) XMAN1, an inner nuclear membrane protein, antagonizes BMP signaling by interacting with Smad1 in xenopus embryos. Development 130(9):1783–1794. doi:10.​1242/​dev.​00401 CrossRefPubMed
18.
Zurück zum Zitat Takebayashi-Suzuki K, Funami J, Tokumori D, Saito A, Watabe T, Miyazono K, Kanda A, Suzuki A (2003) Interplay between the tumor suppressor p53 and TGF beta signaling shapes embryonic body axes in xenopus. Development 130(17):3929–3939. doi:10.1242/dev.00615 CrossRefPubMed Takebayashi-Suzuki K, Funami J, Tokumori D, Saito A, Watabe T, Miyazono K, Kanda A, Suzuki A (2003) Interplay between the tumor suppressor p53 and TGF beta signaling shapes embryonic body axes in xenopus. Development 130(17):3929–3939. doi:10.​1242/​dev.​00615 CrossRefPubMed
21.
Zurück zum Zitat Bastian H, Gruss P (1990) A murine even-skipped homologue, Evx 1, is expressed during early embryogenesis and neurogenesis in a biphasic manner. EMBO J 9(6):1839–1852PubMedPubMedCentral Bastian H, Gruss P (1990) A murine even-skipped homologue, Evx 1, is expressed during early embryogenesis and neurogenesis in a biphasic manner. EMBO J 9(6):1839–1852PubMedPubMedCentral
24.
Zurück zum Zitat Wolf C, Thisse C, Stoetzel C, Thisse B, Gerlinger P, Perrin-Schmitt F (1991) The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the xenopus X-twi and the drosophila twist genes. Dev Biol 143(2):363–373. doi:10.1016/0012-1606(91)90086-I CrossRefPubMed Wolf C, Thisse C, Stoetzel C, Thisse B, Gerlinger P, Perrin-Schmitt F (1991) The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the xenopus X-twi and the drosophila twist genes. Dev Biol 143(2):363–373. doi:10.​1016/​0012-1606(91)90086-I CrossRefPubMed
25.
Zurück zum Zitat Kanai-Azuma M, Kanai Y, Gad JM, Tajima Y, Taya C, Kurohmaru M, Sanai Y, Yonekawa H, Yazaki K, Tam PP, Hayashi Y (2002) Depletion of definitive gut endoderm in Sox17-null mutant mice. Development 129(10):2367–2379PubMed Kanai-Azuma M, Kanai Y, Gad JM, Tajima Y, Taya C, Kurohmaru M, Sanai Y, Yonekawa H, Yazaki K, Tam PP, Hayashi Y (2002) Depletion of definitive gut endoderm in Sox17-null mutant mice. Development 129(10):2367–2379PubMed
26.
Zurück zum Zitat Yasunaga M, Tada S, Torikai-Nishikawa S, Nakano Y, Okada M, Jakt LM, Nishikawa S, Chiba T, Era T, Nishikawa S (2005) Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23(12):1542–1550. doi:10.1038/nbt1167 CrossRefPubMed Yasunaga M, Tada S, Torikai-Nishikawa S, Nakano Y, Okada M, Jakt LM, Nishikawa S, Chiba T, Era T, Nishikawa S (2005) Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23(12):1542–1550. doi:10.​1038/​nbt1167 CrossRefPubMed
27.
Zurück zum Zitat Jones CM, Dale L, Hogan BL, Wright CV, Smith JC (1996) Bone morphogenetic protein-4 (BMP-4) acts during gastrula stages to cause ventralization of xenopus embryos. Development 122(5):1545–1554PubMed Jones CM, Dale L, Hogan BL, Wright CV, Smith JC (1996) Bone morphogenetic protein-4 (BMP-4) acts during gastrula stages to cause ventralization of xenopus embryos. Development 122(5):1545–1554PubMed
30.
Zurück zum Zitat Yasuo H, Lemaire P (2001) Role of goosecoid, xnot and Wnt antagonists in the maintenance of the notochord genetic programme in xenopus gastrulae. Development 128(19):3783–3793PubMed Yasuo H, Lemaire P (2001) Role of goosecoid, xnot and Wnt antagonists in the maintenance of the notochord genetic programme in xenopus gastrulae. Development 128(19):3783–3793PubMed
31.
Zurück zum Zitat Luu O, Nagel M, Wacker S, Lemaire P, Winklbauer R (2008) Control of gastrula cell motility by the goosecoid/mix.1/siamois network: basic patterns and paradoxical effects. Dev Dyn 237(5):1307–1320. doi:10.1002/dvdy.21522 CrossRefPubMed Luu O, Nagel M, Wacker S, Lemaire P, Winklbauer R (2008) Control of gastrula cell motility by the goosecoid/mix.1/siamois network: basic patterns and paradoxical effects. Dev Dyn 237(5):1307–1320. doi:10.​1002/​dvdy.​21522 CrossRefPubMed
33.
Zurück zum Zitat Forghanifard MM, Moaven O, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, Moghbeli M, Nejadsattari T, Parivar K, Abbaszadegan MR (2012) Expression analysis elucidates the roles of MAML1 and Twist1 in esophageal squamous cell carcinoma aggressiveness and metastasis. Ann Surg Oncol 19(3):743–749. doi:10.1245/s10434-011-2074-8 CrossRefPubMed Forghanifard MM, Moaven O, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, Moghbeli M, Nejadsattari T, Parivar K, Abbaszadegan MR (2012) Expression analysis elucidates the roles of MAML1 and Twist1 in esophageal squamous cell carcinoma aggressiveness and metastasis. Ann Surg Oncol 19(3):743–749. doi:10.​1245/​s10434-011-2074-8 CrossRefPubMed
37.
Zurück zum Zitat Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939. doi:10.1016/j.cell.2004.06.006 CrossRefPubMed Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939. doi:10.​1016/​j.​cell.​2004.​06.​006 CrossRefPubMed
38.
Zurück zum Zitat Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, Uchikado Y, Kita Y, Tamotsu K, Sakamoto A, Owaki T, Aikou T (2009) Significance of twist expression and its association with E-cadherin in esophageal squamous cell carcinoma. J Exp Clin Cancer Res 28:158. doi:10.1186/1756-9966-28-158 CrossRefPubMedPubMedCentral Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, Uchikado Y, Kita Y, Tamotsu K, Sakamoto A, Owaki T, Aikou T (2009) Significance of twist expression and its association with E-cadherin in esophageal squamous cell carcinoma. J Exp Clin Cancer Res 28:158. doi:10.​1186/​1756-9966-28-158 CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Yuen HF, Chan YP, Wong ML, Kwok WK, Chan KK, Lee PY, Srivastava G, Law SY, Wong YC, Wang X, Chan KW (2007) Upregulation of twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol 60(5):510–514. doi:10.1136/jcp.2006.039099 CrossRefPubMedPubMedCentral Yuen HF, Chan YP, Wong ML, Kwok WK, Chan KK, Lee PY, Srivastava G, Law SY, Wong YC, Wang X, Chan KW (2007) Upregulation of twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol 60(5):510–514. doi:10.​1136/​jcp.​2006.​039099 CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Du YC, Oshima H, Oguma K, Kitamura T, Itadani H, Fujimura T, Piao YS, Yoshimoto T, Minamoto T, Kotani H, Taketo MM, Oshima M (2009) Induction and down-regulation of Sox17 and its possible roles during the course of gastrointestinal tumorigenesis. Gastroenterology 137(4):1346–1357. doi:10.1053/j.gastro.2009.06.041 CrossRefPubMed Du YC, Oshima H, Oguma K, Kitamura T, Itadani H, Fujimura T, Piao YS, Yoshimoto T, Minamoto T, Kotani H, Taketo MM, Oshima M (2009) Induction and down-regulation of Sox17 and its possible roles during the course of gastrointestinal tumorigenesis. Gastroenterology 137(4):1346–1357. doi:10.​1053/​j.​gastro.​2009.​06.​041 CrossRefPubMed
Metadaten
Titel
Contribution of EVX1 in Aggressiveness of Esophageal Squamous Cell Carcinoma
verfasst von
Afsaneh Javdani Mallak
Mohammad Reza Abbaszadegan
Pegah Naeemi Khorasanizadeh
Mohammad Mahdi Forghanifard
Publikationsdatum
01.04.2016
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 2/2016
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-015-0005-x

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