Journal of Biomedical Science | |
Role of SALL4 in the progression and metastasis of colorectal cancer | |
Mohammad Reza Abbaszadegan6  Samaneh Boroumand-Noughabi5  Afsaneh Javdani Mallak4  Alireza Tavassoli2  Reza Raeisossadati3  Meysam Moghbeli3  Mohammad Mahdi Forghanifard1  | |
[1] Department of Biology, Damghan Branch, Islamic Azad University, Cheshmeh-Ali Boulevard, Sa’dei Square, P.O.Box: 3671639998, Damghan, Iran;Endoscopic and Minimally Invasive Research Center, Qaem Hospital, Mashhad, Iran;Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran;Young Researchers Club and Elites, Mashhad Branch, Islamic Azad University, Mashhad, Iran;Department of Pathology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran;Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran | |
关键词: Self-renewal; Real-time PCR; Expressional analysis; SALL4; Colorectal cancer; | |
Others : 824308 DOI : 10.1186/1423-0127-20-6 |
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received in 2012-11-22, accepted in 2013-01-25, 发布年份 2013 | |
【 摘 要 】
Background
Human cancer cells resemble stem cells in expression signatures leading them to share some features, most notably, self-renewal. A complex network of transcription factors and signaling molecules are required for continuance of this trait. SALL4 is a zinc finger transcriptional activator crucial for maintenance of self-renewal in stem cells; however, its expression level has not yet been elucidated in colorectal tumor cells. To determine this level and probable clinicopathological consequences, its expression was analyzed.
Methods
SALL4 expression in fresh tumoral and distant tumor-free tissues from 46 colorectal samples was compared by real-time polymerase chain reaction (PCR).
Results
Greater than a two-fold increase in SALL4 expression was detected in 87% of tumors vs. normal related tissues. SALL4 expression was significantly correlated with tumor cell metastasis to lymph nodes, especially in moderately-differentiated tumor samples (P < 0.05). Furthermore, higher levels of SALL4 mRNA expression were significantly associated with younger than older patients with tumor cells in stages I and II (P < 0.05).
Conclusions
These results indicate a relationship between SALL4 expression and tumor cell metastasis to lymph nodes and consequent advancement of tumors to advanced stages III and IV. Along with the promising evidence of its role in self-renewal in various cancers, SALL4 may have a role in progression, development and maintenance of colorectal cancers.
【 授权许可】
2013 Forghanifard et al; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
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20140713030402146.pdf | 337KB | download | |
Figure 2. | 60KB | Image | download |
Figure 1. | 55KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
- [2]Gryfe R, Swallow C, Bapat B, Redston M, Gallinger S, Couture J: Molecular biology of colorectal cancer. Curr Probl Cancer 1997, 21:233-300.
- [3]Kohlhase J, Schuh R, Dowe G, Kuhnlein RP, Jackle H, Schroeder B, Schulz-Schaeffer W, Kretzschmar HA, Kohler A, Muller U: Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the Drosophila gene spalt. Genomics 1996, 38:291-298.
- [4]Kuhnlein RP, Schuh R: Dual function of the region-specific homeotic gene spalt during Drosophila tracheal system development. Development 1996, 122:2215-2223.
- [5]Kohlhase J, Heinrich M, Schubert L, Liebers M, Kispert A, Laccone F, Turnpenny P, Winter RM, Reardon W: Okihiro syndrome is caused by SALL4 mutations. Hum Mol Genet 2002, 11:2979-2987.
- [6]Yuri S, Fujimura S, Nimura K, Takeda N, Toyooka Y, Fujimura Y, Aburatani H, Ura K, Koseki H, Niwa H, Nishinakamura R: Sall4 is essential for stabilization, but not for pluripotency, of embryonic stem cells by repressing aberrant trophectoderm gene expression. Stem Cells 2009, 27:796-805.
- [7]Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L: Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol 2006, 8:1114-1123.
- [8]Yang J, Gao C, Chai L, Ma Y: A novel SALL4/OCT4 transcriptional feedback network for pluripotency of embryonic stem cells. PLoS One 2010, 5:e10766.
- [9]Yang J, Chai L, Fowles TC, Alipio Z, Xu D, Fink LM, Ward DC, Ma Y: Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells. Proc Natl Acad Sci USA 2008, 105:19756-19761.
- [10]Ma Y, Cui W, Yang J, Qu J, Di C, Amin HM, Lai R, Ritz J, Krause DS, Chai L: SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice. Blood 2006, 108:2726-2735.
- [11]Shuai X, Zhou D, Shen T, Wu Y, Zhang J, Wang X, Li Q: Overexpression of the novel oncogene SALL4 and activation of the Wnt/beta-catenin pathway in myelodysplastic syndromes. Cancer Genet Cytogenet 2009, 194:119-124.
- [12]Lim CY, Tam WL, Zhang J, Ang HS, Jia H, Lipovich L, Ng HH, Wei CL, Sung WK, Robson P: Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell 2008, 3:543-554.
- [13]Kohlhase J, Heinrich M, Liebers M, Frohlich Archangelo L, Reardon W, Kispert A: Cloning and expression analysis of SALL4, the murine homologue of the gene mutated in Okihiro syndrome. Cytogenet Genome Res 2002, 98:274-277.
- [14]Kobayashi D, Kuribayshi K, Tanaka M, Watanabe N: SALL4 is essential for cancer cell proliferation and is overexpressed at early clinical stages in breast cancer. Int J Oncol 2011, 38:933-939.
- [15]Kobayashi D, Kuribayashi K, Tanaka M, Watanabe N: Overexpression of SALL4 in lung cancer and its importance in cell proliferation. Oncol Rep 2011, 26:965-970.
- [16]Cui W, Kong NR, Ma Y, Amin HM, Lai R, Chai L: Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia. Mod Pathol 2006, 19:1585-1592.
- [17]Forte A, Schettino MT, Finicelli M, Cipollaro M, Colacurci N, Cobellis L, Galderisi U: Expression pattern of stemness-related genes in human endometrial and endometriotic tissues. Mol Med 2009, 15:392-401.
- [18]Cao D, Guo S, Allan RW, Molberg KH, Peng Y: SALL4 is a novel sensitive and specific marker of ovarian primitive germ cell tumors and is particularly useful in distinguishing yolk sac tumor from clear cell carcinoma. Am J Surg Pathol 2009, 33:894-904.
- [19]Cao D, Li J, Guo CC, Allan RW, Humphrey PA: SALL4 is a novel diagnostic marker for testicular germ cell tumors. Am J Surg Pathol 2009, 33:1065-1077.
- [20]Cao D, Humphrey PA, Allan RW: SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors. Cancer 2009, 115:2640-2651.
- [21]Liu A, Cheng L, Du J, Peng Y, Allan RW, Wei L, Li J, Cao D: Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumors. Am J Surg Pathol 2010, 34:697-706.
- [22]Wittekind C, Oberschmid B: TNM classification of malignant tumors 2010: General aspects and amendments in the general section. Pathologe 2010, 31:333-334. 336–338
- [23]Forghanifard MM, Moaven O, Farshchian M, Montazer M, Raeisossadati R, Abdollahi A, Moghbeli M, Nejadsattari T, Parivar K, Abbaszadegan MR: Expression analysis elucidates the roles of MAML1 and Twist1 in esophageal squamous cell carcinoma aggressiveness and metastasis. Ann Surg Oncol 2012, 19:743-749.
- [24]Andersen CL, Jensen JL, Orntoft TF: Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 2004, 64:5245-5250.
- [25]Frei E, Schuh R, Baumgartner S, Burri M, Noll M, Jurgens G, Seifert E, Nauber U, Jackle H: Molecular characterization of spalt, a homeotic gene required for head and tail development in the Drosophila embryo. EMBO J 1988, 7:197-204.
- [26]Liang J, Wan M, Zhang Y, Gu P, Xin H, Jung SY, Qin J, Wong J, Cooney AJ, Liu D, Songyang Z: Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nat Cell Biol 2008, 10:731-739.
- [27]Wu Q, Chen X, Zhang J, Loh YH, Low TY, Zhang W, Zhang W, Sze SK, Lim B, Ng HH: Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. J Biol Chem 2006, 281:24090-24094.
- [28]Gazouli M, Roubelakis MG, Theodoropoulos GE, Papailiou J, Vaiopoulou A, Pappa KI, Nikiteas N, Anagnou NP: OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer. Mol Carcinog 2012, 51:165-173.
- [29]Meng HM, Zheng P, Wang XY, Liu C, Sui HM, Wu SJ, Zhou J, Ding YQ, Li JM: Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther 2010, 16:9(4).
- [30]Xu F, Dai C, Zhang R, Zhao Y, Peng S, Jia C: Nanog: a potential biomarker for liver metastasis of colorectal cancer. Dig Dis Sci 2012, 57(9):2340-2346.
- [31]Yang J, Chai L, Liu F, Fink LM, Lin P, Silberstein LE, Amin HM, Ward DC, Ma Y: Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci USA 2007, 104:10494-10499.
- [32]Rajasekhar VK, Begemann M: Concise review: roles of polycomb group proteins in development and disease: a stem cell perspective. Stem Cells 2007, 25:2498-2510.
- [33]Zhang H, Ye YJ, Cui ZR, Wang S: Mechanism of polycomb Bmi1-targeted therapy for colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi 2011, 14:623-626.
- [34]Yang J, Chai L, Gao C, Fowles TC, Alipio Z, Dang H, Xu D, Fink LM, Ward DC, Ma Y: SALL4 is a key regulator of survival and apoptosis in human leukemic cells. Blood 2008, 112:805-813.
- [35]Guo Y, Mantel C, Hromas RA, Broxmeyer HE: Oct-4 is critical for survival/antiapoptosis of murine embryonic stem cells subjected to stress: effects associated with Stat3/survivin. Stem Cells 2008, 26:30-34.
- [36]Kersseboom R, Dubbink H, Corver W, van Tilburg A, Poley J, van Leerdam M, Atmodimedjo P, van de Laar I, Collee J, Dinjens W: PTEN in colorectal cancer: a report on two Cowden syndrome patients. Clin Genet 2012, 81:555-562.
- [37]Saito Y, Swanson X, Mhashilkar AM, Oida Y, Schrock R, Branch CD, Chada S, Zumstein L, Ramesh R: Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo. Gene Ther 2003, 10:1961-1969.