近日, 國(guó)際知名雜志GUT和Cancer Research接連刊登了中山大學(xué)腫瘤防治中心關(guān)新元教授研究團(tuán)隊(duì)的最新研究成果，文章中,，作者分別對(duì)消化道腫瘤中食管癌和肝癌的發(fā)病機(jī)制進(jìn)行了探索性研究,。
食管癌和肝癌都是嚴(yán)重危害我國(guó)人民健康的惡性腫瘤，預(yù)后相對(duì)差,。關(guān)新元教授率領(lǐng)研究團(tuán)隊(duì)對(duì)上述兩種腫瘤進(jìn)行了深入細(xì)致的研究工作,。分別從腫瘤發(fā)生的遺傳學(xué)基礎(chǔ)和腫瘤細(xì)胞生長(zhǎng)的微環(huán)境為立足點(diǎn)對(duì)腫瘤的發(fā)生機(jī)制進(jìn)行了研究?！⊙芯堪l(fā)現(xiàn),，食管鱗狀細(xì)胞癌的腫瘤相關(guān)成纖維細(xì)胞能夠分泌WNT2促進(jìn)腫瘤細(xì)胞生長(zhǎng)，這種效應(yīng)是通過激活WNT2/beta-catenin通路發(fā)揮作用的（GUT 2011, 60(12): 1635-43 ）,。除環(huán)境因素以外,，遺傳因素在食管癌的發(fā)生中也起到重要作用。研究團(tuán)隊(duì)發(fā)現(xiàn)在食管鱗狀細(xì)胞癌患者中多數(shù)出現(xiàn)抑癌基因RBMS3的表達(dá)下調(diào),，深入研究發(fā)現(xiàn),，該基因可以下調(diào)c-Myc，進(jìn)而影響Rb的磷酸化而發(fā)揮抑癌功能,，該基因在患者腫瘤組織中的表達(dá)情況與患者的預(yù)后顯著相關(guān),，研究結(jié)果發(fā)表于Cancer Research 2011, 71(19): 6106-15。
此外,，關(guān)新元教授研究團(tuán)隊(duì)還發(fā)現(xiàn)CHD1L與肝癌治療的化療耐藥有關(guān),，并構(gòu)建了針對(duì)CHD1L的腺病毒攜帶的干擾載體，體內(nèi),、體外試驗(yàn)結(jié)果表明,，降低CHD1L表達(dá)后能夠顯著增加肝癌細(xì)胞對(duì)化療藥物的敏感性,，取得很好的療效（GUT 2011, 60(4): 534-43）。
關(guān)新元教授主持的基于實(shí)驗(yàn)研究基礎(chǔ)之上系列消化道腫瘤研究立足于找到能夠?qū)εR床的診斷具有指導(dǎo)意義的新的標(biāo)志物,，并為治療探索新的依據(jù)和新的思路,、方法。（生物谷Bioon.com）
doi:10.1136/gut.2011.241638
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Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway.
Li Fu1,2, Chunyu Zhang3, Li-Yi Zhang2, Sui-Sui Dong2, Lu-Hui Lu2, Juan Chen2, Yongdong Dai1, Yan Li1, Kar Lok Kong2, Dora L Kwong2, Xin-Yuan Guan1,2
Objectives Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour–stroma interaction. Methods Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2(+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 200× microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial–mesenchymal transition. Conclusions TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.
doi:10.1158/0008-5472.CAN-10-4291
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Downregulation of RBMS3 Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma
Yan Li1, Leilei Chen2, Chang-jun Nie1, Ting-ting Zeng1, Haibo Liu1, Xueying Mao1, Yanru Qin3, Ying-Hui Zhu1, Li Fu2, and Xin-Yuan Guan1,2
Deletions on chromosome 3p occur often in many solid tumors, including esophageal squamous cell carcinoma (ESCC), suggesting the existence at this location of one or more tumor suppressor genes (TSG). In this study, we characterized RBMS3 gene encoding an RNA-binding protein as a candidate TSG located at 3p24. Downregulation of RBMS3 mRNA and protein levels was documented in approximately 50% of the primary ESCCs examined. Clinical association studies determined that RBMS3 downregulation was associated with poor clinical outcomes. RBMS3 expression effectively suppressed the tumorigenicity of ESCC cells in vitro and in vivo, including by inhibition of cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. Molecular analyses revealed that RBMS3 downregulated c-Myc and CDK4, leading to subsequent inhibition of Rb phosphorylation. Together, our findings suggest a tumor suppression function for the human RBMS3 gene in ESCC, acting through c-Myc downregulation, with genetic loss of this gene in ESCC contributing to poor outcomes in this deadly disease. ,、
