• 上海交通大學(xué)附屬第三人民醫(yī)院普外科（上海 201900）;

目的介紹上皮間質(zhì)轉(zhuǎn)化（EMT）在胃腸道腫瘤中的研究現(xiàn)狀。 方法收集近年來國內(nèi)、外有關(guān)EMT及其調(diào)節(jié)因子與胃腸道腫瘤關(guān)系的文獻(xiàn)并作綜述。 結(jié)果 EMT是胚胎發(fā)育的一個(gè)基本過程，在成熟上皮細(xì)胞中EMT的異常激活可以降低細(xì)胞間黏附分子表達(dá)進(jìn)而促進(jìn)腫瘤的轉(zhuǎn)移。上皮細(xì)胞表面標(biāo)志物E鈣黏素表達(dá)抑制和EMT發(fā)生密切相關(guān)，E-鈣黏素轉(zhuǎn)錄抑制因子可能在調(diào)節(jié)EMT過程中起重要作用，并且這些轉(zhuǎn)錄抑制因子在胃腸道腫瘤中呈明顯高表達(dá)。 此外，EMT的發(fā)生可能在胃腸道腫瘤干細(xì)胞形成過程中起重要作用。結(jié)論 EMT及其調(diào)節(jié)因子在胃腸道腫瘤發(fā)生、侵襲和轉(zhuǎn)移過程中起了重要作用，對(duì)于EMT及其調(diào)節(jié)因子的研究可以為腫瘤發(fā)生機(jī)理提供新的視角，為腫瘤治療提供新的靶點(diǎn)。

引用本文： 蔡成,俞繼衛(wèi),姜波健. 上皮-間質(zhì)轉(zhuǎn)化在胃腸道腫瘤中的研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(11): 1234-F3. doi: 復(fù)制

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2. Kong D, Li Y, Wang Z, et al. Cancer stem cells and epithelialtomesenchymal transition (EMT)phenotypic cells: are they cousins or twins? [J]. Cancers, 2011, 3(1): 716729.
3. Pasqua Ferrara A, Scalera I, Rotelli MT, et al. Stem cells and colorectal cancerogenesis: new insight [J]. Minerva Chir, 2010, 65(2): 235242.
4. Wellner U, Schubert J, Burk UC, et al. The EMTactivator ZEB1 promotes tumorigenicity by repressing stemnessinhibiting microRNAs [J]. Nat Cell Biol, 2009, 11(12): 14871495.
5. Kalluri R, Weinberg RA. The basics of epithelialmesenchymal transition [J]. J Clin Invest, 2009, 119(6): 14201428.
6. Kang H, Min BS, Lee KY, et al. Loss of Ecadherin and MUC2 expressions correlated with poor survival in patients with stages Ⅱ and Ⅲ colorectal carcinoma [J]. Ann Surg Oncol, 2011, 18(3): 711719.
7. Mimata A, Fukamachi H, Eishi Y, et al. Loss of Ecadherin in mouse gastric epithelial cells induces signet ringlike cells, a possible precursor lesion of diffuse gastric cancer [J]. Cancer Sci, 2011, 102(5): 942950.
8. Pryczynicz A, GuzińskaUstymowicz K, Kemona A, et al. Expression of the Ecadherincatenin complex in patients with pancreatic ductal adenocarcinoma [J]. Folia Histochem Cytobiol, 2010, 48(1): 128133.
9. Huang WY, Yang PM, Chang YF, et al. Methotrexate induces apoptosis through p53/p21dependent pathway and increases Ecadherin expression through downregulation of HDAC/EZH2 [J]. Biochem Pharmacol, 2011, 81(4): 510517.
10. Natalwala A, Spychal R, Tselepis C. Epithelialmesenchymal transition mediated tumourigenesis in the gastrointestinal tract [J]. World J Gastroenterol， 2008， 14(24): 37923797.
11. Lee MY, Chou CY, Tang MJ, et al. Epithelialmesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail upregulation [J]. Clin Cancer Res, 2008, 14(15): 47434750.
12. Zeisberg M, Neilson EG. Biomarkers for epithelialmesenchymal transitions [J]. J Clin Invest, 2009, 119(6): 14291437.
13. Yang J, Eddy JA, Pan Y, et al. Integrated proteomics and genomics analysis reveals a novel mesenchymal to epithelial reverting transition in leiomyosarcoma through regulation of slug [J]. Mol Cell Proteomics, 2010, 9(11): 24052413.
14. PérezMancera PA, GonzálezHerrero I, Maclean K, et al. SLUG (SNAI2) overexpression in embryonic development [J]. Cytogenet Genome Res, 2006, 114(1): 2429.
15. Clarhaut J, Gemmill RM, Potiron VA, et al. ZEB1, a repressor of the semaphorin 3F tumor suppressor gene in lung cancer cells [J]. Neoplasia, 2009, 11(2): 157166.
16. Oztas E, Avci ME, Ozcan A, et al. Novel monoclonal antibodies detect Smadinteracting protein 1 (SIP1) in the cytoplasm of human cells from multiple tumor tissue arrays [J]. Exp Mol Pathol, 2010, 89(2): 182189.
17. Xia M, Hu M, Wang J, et al. Identification of the role of Smad interacting protein 1 (SIP1) in glioma [J]. J Neurooncol, 2010, 97(2): 225232.
18. Luo GQ, Li JH, Wen JF, et al. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells [J]. World J Gastroenterol, 2008, 14(16): 24872493.
19. Du C, Zhang C, Hassan S, et al. Protein kinase D1 suppresses epithelialtomesenchymal transition through phosphorylation of snail [J]. Cancer Res， 2010, 70(20): 78107819.
20. 唐志鋒, 周永寧, 蘇曉娟, 等. Snail與Ecadherin在胃癌中的表達(dá)及臨床意義 [J]. 中國急救復(fù)蘇與災(zāi)害醫(yī)學(xué)雜志， 2010, 5(8): 696699.
21. Castro Alves C, Rosivatz E, Schott C, et al. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the downregulation of Ecadherin [J]. J Pathol, 2007, 211(5): 507515.
22. Feng MY, Wang K, Song HT, et al. Metastasisinduction and apoptosisprotection by TWIST in gastric cancer cells [J]. Clin Exp Metastasis, 2009, 26(8): 10131023.
23. Yang Z, Zhang X, Gang H, et al. Upregulation of gastric cancer cell invasion by Twist is accompanied by Ncadherin and fibronectin expression [J]. Biochem Biophys Res Commun， 2007， 358(3): 925930.
24. Lee S, Bang S, Song K, et al. Differential expression in normaladenomacarcinoma sequence suggests complex molecular carcinogenesis in colon [J]. Oncol Rep, 2006, 16(4): 747754.
25. Bottomly D, Kyler SL, McWeeney SK, et al. Identification of (beta)catenin binding regions in colon cancer cells using ChIPSeq [J]. Nucleic Acids Res， 2010, 38(17): 57355745.
26. Kuphal F, Behrens J. Ecadherin modulates Wntdependent transcription in colorectal cancer cells but does not alter Wntindependent gene expression in fibroblasts [J]. Exp Cell Res, 2006, 312(4): 457467.
27. 鄭伯安, 鄧高里, 董全進(jìn), 等. 表皮鈣黏附素和Snail蛋白的表達(dá)與大腸癌侵襲轉(zhuǎn)移及預(yù)后的關(guān)系 [J]. 中華腫瘤雜志， 2010， 2010, 32(2): 111116.
28. Shioiri M, Shida T, Koda K, et al. Slug expression is an independent prognostic parameter for poor survival in colorectalcarcinoma patients [J]. Br J Cancer, 2006, 94(12): 18161822.
29. ValdésMora F, Gómez del Pulgar T, Bandrés E, et al. TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectal cancer [J]. Ann Surg Oncol, 2009, 16(1): 7887.
30. Anderson EC, Hessman C, Levin TG, et al. The role of colorectal cancer stem cells in metastatic disease and therapeutic response [J]. Cancer， 2011, 3(1): 319339.
31. May CD, Sphyris N, Evans KW, et al. Epithelialmesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression [J]. Breast Cancer Res, 2011, 13(1): 202.
32. Hollier BG, Evans K, Mani SA. The epithelialtomesenchymal transition and cancer stem cells: a coalition against cancer therapies [J]. J Mammary Gland Biol Neoplasia, 2009, 14(1): 2943.
33. Mani SA, Guo W, Liao MJ, et al. The epithelialmesenchymal transition generates cells with properties of stem cells [J]. Cell, 2008, 133(4): 704715.
34. Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer [J]. Cell Stem Cell, 2007, 1(3): 313323.
35. Na DC, Lee JE, Yoo JE, et al. Invasion and EMTassociated genes are upregulated in B viral hepatocellular carcinoma with high expression of CD133human and cell culture study [J]. Exp Mol Pathol, 2011, 90(1): 6673.
  1. 1. Thiery JP, Sleeman JP. Complex networks orchestrate epithelialmesenchymal transitions [J]. Nat Rev Mol Cell Biol, 2006, 7(2): 131142.
  2. 2. Kong D, Li Y, Wang Z, et al. Cancer stem cells and epithelialtomesenchymal transition (EMT)phenotypic cells: are they cousins or twins? [J]. Cancers, 2011, 3(1): 716729.
  3. 3. Pasqua Ferrara A, Scalera I, Rotelli MT, et al. Stem cells and colorectal cancerogenesis: new insight [J]. Minerva Chir, 2010, 65(2): 235242.
  4. 4. Wellner U, Schubert J, Burk UC, et al. The EMTactivator ZEB1 promotes tumorigenicity by repressing stemnessinhibiting microRNAs [J]. Nat Cell Biol, 2009, 11(12): 14871495.
  5. 5. Kalluri R, Weinberg RA. The basics of epithelialmesenchymal transition [J]. J Clin Invest, 2009, 119(6): 14201428.
  6. 6. Kang H, Min BS, Lee KY, et al. Loss of Ecadherin and MUC2 expressions correlated with poor survival in patients with stages Ⅱ and Ⅲ colorectal carcinoma [J]. Ann Surg Oncol, 2011, 18(3): 711719.
  7. 7. Mimata A, Fukamachi H, Eishi Y, et al. Loss of Ecadherin in mouse gastric epithelial cells induces signet ringlike cells, a possible precursor lesion of diffuse gastric cancer [J]. Cancer Sci, 2011, 102(5): 942950.
  8. 8. Pryczynicz A, GuzińskaUstymowicz K, Kemona A, et al. Expression of the Ecadherincatenin complex in patients with pancreatic ductal adenocarcinoma [J]. Folia Histochem Cytobiol, 2010, 48(1): 128133.
  9. 9. Huang WY, Yang PM, Chang YF, et al. Methotrexate induces apoptosis through p53/p21dependent pathway and increases Ecadherin expression through downregulation of HDAC/EZH2 [J]. Biochem Pharmacol, 2011, 81(4): 510517.
  10. 10. Natalwala A, Spychal R, Tselepis C. Epithelialmesenchymal transition mediated tumourigenesis in the gastrointestinal tract [J]. World J Gastroenterol， 2008， 14(24): 37923797.
  11. 11. Lee MY, Chou CY, Tang MJ, et al. Epithelialmesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail upregulation [J]. Clin Cancer Res, 2008, 14(15): 47434750.
  12. 12. Zeisberg M, Neilson EG. Biomarkers for epithelialmesenchymal transitions [J]. J Clin Invest, 2009, 119(6): 14291437.
  13. 13. Yang J, Eddy JA, Pan Y, et al. Integrated proteomics and genomics analysis reveals a novel mesenchymal to epithelial reverting transition in leiomyosarcoma through regulation of slug [J]. Mol Cell Proteomics, 2010, 9(11): 24052413.
  14. 14. PérezMancera PA, GonzálezHerrero I, Maclean K, et al. SLUG (SNAI2) overexpression in embryonic development [J]. Cytogenet Genome Res, 2006, 114(1): 2429.
  15. 15. Clarhaut J, Gemmill RM, Potiron VA, et al. ZEB1, a repressor of the semaphorin 3F tumor suppressor gene in lung cancer cells [J]. Neoplasia, 2009, 11(2): 157166.
  16. 16. Oztas E, Avci ME, Ozcan A, et al. Novel monoclonal antibodies detect Smadinteracting protein 1 (SIP1) in the cytoplasm of human cells from multiple tumor tissue arrays [J]. Exp Mol Pathol, 2010, 89(2): 182189.
  17. 17. Xia M, Hu M, Wang J, et al. Identification of the role of Smad interacting protein 1 (SIP1) in glioma [J]. J Neurooncol, 2010, 97(2): 225232.
  18. 18. Luo GQ, Li JH, Wen JF, et al. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells [J]. World J Gastroenterol, 2008, 14(16): 24872493.
  19. 19. Du C, Zhang C, Hassan S, et al. Protein kinase D1 suppresses epithelialtomesenchymal transition through phosphorylation of snail [J]. Cancer Res， 2010, 70(20): 78107819.
  20. 20. 唐志鋒, 周永寧, 蘇曉娟, 等. Snail與Ecadherin在胃癌中的表達(dá)及臨床意義 [J]. 中國急救復(fù)蘇與災(zāi)害醫(yī)學(xué)雜志， 2010, 5(8): 696699.
  21. 21. Castro Alves C, Rosivatz E, Schott C, et al. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the downregulation of Ecadherin [J]. J Pathol, 2007, 211(5): 507515.
  22. 22. Feng MY, Wang K, Song HT, et al. Metastasisinduction and apoptosisprotection by TWIST in gastric cancer cells [J]. Clin Exp Metastasis, 2009, 26(8): 10131023.
  23. 23. Yang Z, Zhang X, Gang H, et al. Upregulation of gastric cancer cell invasion by Twist is accompanied by Ncadherin and fibronectin expression [J]. Biochem Biophys Res Commun， 2007， 358(3): 925930.
  24. 24. Lee S, Bang S, Song K, et al. Differential expression in normaladenomacarcinoma sequence suggests complex molecular carcinogenesis in colon [J]. Oncol Rep, 2006, 16(4): 747754.
  25. 25. Bottomly D, Kyler SL, McWeeney SK, et al. Identification of (beta)catenin binding regions in colon cancer cells using ChIPSeq [J]. Nucleic Acids Res， 2010, 38(17): 57355745.
  26. 26. Kuphal F, Behrens J. Ecadherin modulates Wntdependent transcription in colorectal cancer cells but does not alter Wntindependent gene expression in fibroblasts [J]. Exp Cell Res, 2006, 312(4): 457467.
  27. 27. 鄭伯安, 鄧高里, 董全進(jìn), 等. 表皮鈣黏附素和Snail蛋白的表達(dá)與大腸癌侵襲轉(zhuǎn)移及預(yù)后的關(guān)系 [J]. 中華腫瘤雜志， 2010， 2010, 32(2): 111116.
  28. 28. Shioiri M, Shida T, Koda K, et al. Slug expression is an independent prognostic parameter for poor survival in colorectalcarcinoma patients [J]. Br J Cancer, 2006, 94(12): 18161822.
  29. 29. ValdésMora F, Gómez del Pulgar T, Bandrés E, et al. TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectal cancer [J]. Ann Surg Oncol, 2009, 16(1): 7887.
  30. 30. Anderson EC, Hessman C, Levin TG, et al. The role of colorectal cancer stem cells in metastatic disease and therapeutic response [J]. Cancer， 2011, 3(1): 319339.
  31. 31. May CD, Sphyris N, Evans KW, et al. Epithelialmesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression [J]. Breast Cancer Res, 2011, 13(1): 202.
  32. 32. Hollier BG, Evans K, Mani SA. The epithelialtomesenchymal transition and cancer stem cells: a coalition against cancer therapies [J]. J Mammary Gland Biol Neoplasia, 2009, 14(1): 2943.
  33. 33. Mani SA, Guo W, Liao MJ, et al. The epithelialmesenchymal transition generates cells with properties of stem cells [J]. Cell, 2008, 133(4): 704715.
  34. 34. Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer [J]. Cell Stem Cell, 2007, 1(3): 313323.
  35. 35. Na DC, Lee JE, Yoo JE, et al. Invasion and EMTassociated genes are upregulated in B viral hepatocellular carcinoma with high expression of CD133human and cell culture study [J]. Exp Mol Pathol, 2011, 90(1): 6673.