Research progress about the molecular mechanism of liver metastasis from colorectal cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUI Peng ¹ , LIU Lianxin ² ,  LIANG Yingjian ¹

1. Department of Liver Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China;
2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China , Hefei 230036, P. R. China;

Corresponding author：

LIANG Yingjian, Email: genomeliang@sina.com

Keywords：

colorectal cancer; liver metastasis; research progress

DOI：

10.7507/1007-9424.201812046

Video：

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Objective To summarize the papers about the molecular mechanisms of liver metastasis from colorectal cancer in recent years and in order to provide assistance for the diagnosis and treatment of liver metastases from colorectal cancer.Method The relevant literatures at home and abroad in recent years about the molecular mechanisms of liver metastasis from colorectal cancer were reviewed.Results The molecular mechanism of liver metastasis from colorectal cancer is complicated. For example, microRNA-192 could inhibit liver metastasis from colorectal cancer through multiple targets, however microRNA-181a could promote liver metastasis from colorectal cancer. TGF-β inhibits liver metastasis from colorectal cancer by inhibiting cell proliferation and Smad-dependent signaling to induce apoptosis. Elevated CEA level not only help in the diagnosis of colorectal cancer, but also as a prognostic indicator for colorectal cancer patients. CEA could promote liver metastasis by affecting the survival of colorectal cancer cells in vessels, changeing the liver microenvironment, and affecting the adhesion and survival of circulating tumor cells in the liver.Conclusions The molecular mechanism of liver metastasis of colorectal cancer has not been fully elucidated. Through in-depth study of the mechanism of liver metastasis of colorectal cancer, it can provide molecular targets for targeted therapy in patients with liver metastases from colorectal cancer, such as bevacizumab, cetuximab, panitumab and so on. Detecting the change of serological markers in patients with colorectal cancer can help diagnose, judge recurrence, prognosis and metastasis.

Citation： HUI Peng, LIU Lianxin, LIANG Yingjian. Research progress about the molecular mechanism of liver metastasis from colorectal cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(6): 758-763. doi: 10.7507/1007-9424.201812046 Copy

1.	Huang X, Zou Y, Lian L, et al. Changes of T Cells and cytokines TGF-β1 and IL-10 in mice during liver metastasis of colon carcinoma: implications for liver anti-tumor immunity. Gastrointest Surg, 2013, 17(7): 1283-1291.
2.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3.	中华人民共和国国家卫生和计划生育委员会医政医管局, 中华医学会肿瘤学分会. 中国结直肠癌诊疗规范 (2017) 版. 中国实用外科杂志, 2018, 38(10): 1089-1103.
4.	中华医学会外科分会胃肠外科学组, 中华医学会外科分会结直肠外科学组, 中国抗癌协会大肠癌专业委员会, 等. 中国结直肠癌肝转移诊断和综合治疗指南 (Ⅴ2018). 中华结直肠疾病电子杂志, 2018, 7(4): 302-314.
5.	Li Z, Wang H, Xu Z, et al. Expression and mechanism of microRNA-181A on incidence and survival in late liver metastases of colorectal cancer. Oncol Rep, 2016, 35(3): 1403-1408.
6.	Chen W, Lin G, Yao Y, et al. MicroRNA hsa-let-7e-5p as a potential prognosis marker for rectal carcinoma with liver metastases. Oncol Lett, 2018, 15(5): 6913-6924.
7.	Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell, 2009, 136(2): 215-233.
8.	Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 2005, 120(1): 15-20.
9.	Tian Q, Liang L, Ding J, et al. MicroRNA-550a acts as a pro-metastatic gene and directly targets cytoplasmic polyadenylation element-binding protein 4 in hepatocellular carcinoma. PloS One, 2012, 7(11): e48958.
10.	Fang L, Du WW, Yang W, et al. MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell cycle, 2012, 11(23): 4352-4365.
11.	Geng L, Chaudhuri A, Talmon G, et al. MicroRNA-192 suppresses liver metastasis of colon cancer. Oncogene, 2014, 33(46): 5332-5340.
12.	Zhang Y, He X, Liu Y, et al. MicroRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metastasis in colorectal cancer. Oncol Rep, 2012, 27(3): 685-694.
13.	Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell, 1998, 92(6): 735-745.
14.	Parikh AA, Fan F, Liu WB, et al. Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol, 2004, 164(6): 2139-2151.
15.	Ji D, Chen Z, Li M, et al. MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1. Mol Cancer, 2014, 13(1): 86.
16.	Zhang X, Gaspard JP, Chung DC. Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia. Cancer Res, 2001, 61(16): 6050-6054.
17.	冯磊, 徐明清. miR-203 与肿瘤关系的研究进展. 中国普外基础与临床杂志, 2017, 24(2): 259-263.
18.	Yuan Y, Zeng ZY, Liu XH, et al. MicroRNA-203 inhibits cell proliferation by repressing ΔNp63 expression in human esophageal squamous cell carcinoma. BMC Cancer, 2011, 11: 57.
19.	靖琳, 任建琳, 季青, 等. 长链非编码 RNA 调控结直肠癌侵袭与转移机制的研究进展. 国际消化病杂志, 2015, 35(5): 334-337.
20.	靳雪芹, 卢忠心. 长链非编码 RNA 与肿瘤研究进展. 国际检验医学杂志, 2018, 39(12): 1492-1495.
21.	Sun J, Hu J, Wang G, et al. LncRNA TUG1 promoted KIAA1199 expression via miR-600 to accelerate cell metastasis and epithelial-mesenchymal transition in colorectal cancer. J Exp Clin Cancer Res, 2018, 37(1): 106.
22.	Xie CR, Wang F, Zhang S, et al. Long Noncoding RNA HCAL facilitates the growth and metastasis of hepatocellular carcinoma by acting as a ceRNA of LAPTM4B. Mol Ther Nucleic Acids, 2017, 9: 440-451.
23.	EI Helou R, Pinna G, Cabaud O, et al. miR-600 Acts as a Bimodal Switch that Regulates Breast CancerStem Cell Fate through WNT Signaling. Cell Rep, 2017, 18(9): 2256-2268.
24.	Zhang P, Zuo Z, Wu A, et al. miR-600 inhibits cell proliferation, migration and invasion by targeting p53 in mutant p53-expressing human colorectal cancer cell lines. Oncol Lett, 2017, 13(3): 1789-1796.
25.	McLean MH, Murray GI, Stewart KN, et al. The inflammatory microenvironment in colorectal neoplasia. PLoS One, 2011, 6(1): e15366.
26.	Nagarsheth N, Wicha MS, Zou W, et al. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev immounol, 2017, 17(9): 559-572.
27.	Frick VO, Rubie C, Keilholz U, et al. Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectalmalignancy: An overview. World J Gastroenterol, 2016, 22(2): 833-41.
28.	Liu J, Zhang N, Li Q, et al. Tumor-associated macrophages recruit CCR6+regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS One, 2011, 6(4): e19495.
29.	Yu X, Yuan Z, Yang Z, et al. The novel long noncoding RNA u50535 promotes colorectal cancer growth and metastasis by regulating CCL20. Cell Death Dis, 2018, 9(7): 751.
30.	Cheng XS, Li YF, Tan J, et al. CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition. Cancer Lett, 2014, 348(1-2): 77-87.
31.	Brand S, Olszak T, Beigel F, et al. Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells. J Cell Biochem, 2006, 97(4): 709-723.
32.	Yu J, Han Z, Sun Z, et al. LncRNA SLCO4A1-AS1 facilitates growth and metastasis of colorectal cancer through beta-catenin-dependent Wnt pathway. J Exp Clin Cancer Res, 2018, 37(1): 222.
33.	Zhang B, Halder SK, Zhang S, et al. Targeting transforming growth factor-beta signaling in liver metastasis of colon cancer. Cancer Lett, 2009, 277(1): 114-120.
34.	Li Y, Cao H, Jiao Z, et al. Carcinoembryonic antigen interacts with TGF-β receptor and inhibits TGF-β signaling in colorectal cancers. Cancer Res, 2010, 70(20): 8159-8168.
35.	Are C, Simms N, Rajput A, et al. The role of transforming growth factor-beta in suppression of hepatic metastasis from colon cancer. HPB(Oxford), 2010, 12(7): 498-506.
36.	Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell, 2003, 113(6): 685-700.
37.	Hoosein NM, McKnight MK, Levine AE, et al. Differential sensitivity of subclasses of human colon carcinoma cell lines to the growth inhibitory effects of transforming growth factor-beta 1. Exp Cell Res, 1989, 181(2): 442-453.
38.	Gonzalez-Zubeldia I, Dotor J, Redrado M, et al. Co-migration of colon cancer cells and CAFs induced by TGFbeta(1) enhances liver metastasis. Cell Tissue Res, 2015, 359(3): 829-839.
39.	Villalba M, Evans SR, Vidal-Vanaclocha F, et al. Role of TGF-beta in metastatic colon cancer: it is finally time for targeted therapy. Cell Tissue Res, 2017, 370(1): 29-39.
40.	Calon A, Tauriello DV, Batlle E. TGF-βin CAF-mediated tumor growth and metastasis. Semin Cancer Biol, 2014, 25: 15-22.
41.	Cheng D, Zhao S, Tang H, et al. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4. Oncotarget, 2016, 7(29): 45199-45213.
42.	Itatani Y, Kawada K, Fujishita T, et al. Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1 ⁺ myeloid cells and facilitate liver metastasis. Gastroenterology, 2013, 145(5): 1064-1075.
43.	Stiksma J, Grootendorst DC, van der Linden PW. CA 19-9 As a Marker in Addition to CEA to Monitor Colorectal Cancer. Clin Colorectal Cancer, 2014, 13(4): 239-244.
44.	Ilantzis C, Demarte L, Screaton RA, et al. Deregulated expression of the human tumor marker CEA and CEA family member CEACAM6 disrupts tissue architecture and blocks colonocyte differentiation. Neoplasia, 2002, 4(2): 151-163.
45.	Lee JH, Lee SW. The roles of carcinoembryonic antigen in liver metastasis and therapeutic approaches. Gastroenterol Res Pract, 2017, 2017: 7521987.
46.	Hostetter RB, Augustus LB, Mankarious R, et al. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. J Nati Cancer inst, 1990, 82(5): 380-385.

1. Huang X, Zou Y, Lian L, et al. Changes of T Cells and cytokines TGF-β1 and IL-10 in mice during liver metastasis of colon carcinoma: implications for liver anti-tumor immunity. Gastrointest Surg, 2013, 17(7): 1283-1291.
2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3. 中华人民共和国国家卫生和计划生育委员会医政医管局, 中华医学会肿瘤学分会. 中国结直肠癌诊疗规范 (2017) 版. 中国实用外科杂志, 2018, 38(10): 1089-1103.
4. 中华医学会外科分会胃肠外科学组, 中华医学会外科分会结直肠外科学组, 中国抗癌协会大肠癌专业委员会, 等. 中国结直肠癌肝转移诊断和综合治疗指南 (Ⅴ2018). 中华结直肠疾病电子杂志, 2018, 7(4): 302-314.
5. Li Z, Wang H, Xu Z, et al. Expression and mechanism of microRNA-181A on incidence and survival in late liver metastases of colorectal cancer. Oncol Rep, 2016, 35(3): 1403-1408.
6. Chen W, Lin G, Yao Y, et al. MicroRNA hsa-let-7e-5p as a potential prognosis marker for rectal carcinoma with liver metastases. Oncol Lett, 2018, 15(5): 6913-6924.
7. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell, 2009, 136(2): 215-233.
8. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 2005, 120(1): 15-20.
9. Tian Q, Liang L, Ding J, et al. MicroRNA-550a acts as a pro-metastatic gene and directly targets cytoplasmic polyadenylation element-binding protein 4 in hepatocellular carcinoma. PloS One, 2012, 7(11): e48958.
10. Fang L, Du WW, Yang W, et al. MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell cycle, 2012, 11(23): 4352-4365.
11. Geng L, Chaudhuri A, Talmon G, et al. MicroRNA-192 suppresses liver metastasis of colon cancer. Oncogene, 2014, 33(46): 5332-5340.
12. Zhang Y, He X, Liu Y, et al. MicroRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metastasis in colorectal cancer. Oncol Rep, 2012, 27(3): 685-694.
13. Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell, 1998, 92(6): 735-745.
14. Parikh AA, Fan F, Liu WB, et al. Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol, 2004, 164(6): 2139-2151.
15. Ji D, Chen Z, Li M, et al. MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1. Mol Cancer, 2014, 13(1): 86.
16. Zhang X, Gaspard JP, Chung DC. Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia. Cancer Res, 2001, 61(16): 6050-6054.
17. 冯磊, 徐明清. miR-203 与肿瘤关系的研究进展. 中国普外基础与临床杂志, 2017, 24(2): 259-263.
18. Yuan Y, Zeng ZY, Liu XH, et al. MicroRNA-203 inhibits cell proliferation by repressing ΔNp63 expression in human esophageal squamous cell carcinoma. BMC Cancer, 2011, 11: 57.
19. 靖琳, 任建琳, 季青, 等. 长链非编码 RNA 调控结直肠癌侵袭与转移机制的研究进展. 国际消化病杂志, 2015, 35(5): 334-337.
20. 靳雪芹, 卢忠心. 长链非编码 RNA 与肿瘤研究进展. 国际检验医学杂志, 2018, 39(12): 1492-1495.
21. Sun J, Hu J, Wang G, et al. LncRNA TUG1 promoted KIAA1199 expression via miR-600 to accelerate cell metastasis and epithelial-mesenchymal transition in colorectal cancer. J Exp Clin Cancer Res, 2018, 37(1): 106.
22. Xie CR, Wang F, Zhang S, et al. Long Noncoding RNA HCAL facilitates the growth and metastasis of hepatocellular carcinoma by acting as a ceRNA of LAPTM4B. Mol Ther Nucleic Acids, 2017, 9: 440-451.
23. EI Helou R, Pinna G, Cabaud O, et al. miR-600 Acts as a Bimodal Switch that Regulates Breast CancerStem Cell Fate through WNT Signaling. Cell Rep, 2017, 18(9): 2256-2268.
24. Zhang P, Zuo Z, Wu A, et al. miR-600 inhibits cell proliferation, migration and invasion by targeting p53 in mutant p53-expressing human colorectal cancer cell lines. Oncol Lett, 2017, 13(3): 1789-1796.
25. McLean MH, Murray GI, Stewart KN, et al. The inflammatory microenvironment in colorectal neoplasia. PLoS One, 2011, 6(1): e15366.
26. Nagarsheth N, Wicha MS, Zou W, et al. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev immounol, 2017, 17(9): 559-572.
27. Frick VO, Rubie C, Keilholz U, et al. Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectalmalignancy: An overview. World J Gastroenterol, 2016, 22(2): 833-41.
28. Liu J, Zhang N, Li Q, et al. Tumor-associated macrophages recruit CCR6+regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS One, 2011, 6(4): e19495.
29. Yu X, Yuan Z, Yang Z, et al. The novel long noncoding RNA u50535 promotes colorectal cancer growth and metastasis by regulating CCL20. Cell Death Dis, 2018, 9(7): 751.
30. Cheng XS, Li YF, Tan J, et al. CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition. Cancer Lett, 2014, 348(1-2): 77-87.
31. Brand S, Olszak T, Beigel F, et al. Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells. J Cell Biochem, 2006, 97(4): 709-723.
32. Yu J, Han Z, Sun Z, et al. LncRNA SLCO4A1-AS1 facilitates growth and metastasis of colorectal cancer through beta-catenin-dependent Wnt pathway. J Exp Clin Cancer Res, 2018, 37(1): 222.
33. Zhang B, Halder SK, Zhang S, et al. Targeting transforming growth factor-beta signaling in liver metastasis of colon cancer. Cancer Lett, 2009, 277(1): 114-120.
34. Li Y, Cao H, Jiao Z, et al. Carcinoembryonic antigen interacts with TGF-β receptor and inhibits TGF-β signaling in colorectal cancers. Cancer Res, 2010, 70(20): 8159-8168.
35. Are C, Simms N, Rajput A, et al. The role of transforming growth factor-beta in suppression of hepatic metastasis from colon cancer. HPB(Oxford), 2010, 12(7): 498-506.
36. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell, 2003, 113(6): 685-700.
37. Hoosein NM, McKnight MK, Levine AE, et al. Differential sensitivity of subclasses of human colon carcinoma cell lines to the growth inhibitory effects of transforming growth factor-beta 1. Exp Cell Res, 1989, 181(2): 442-453.
38. Gonzalez-Zubeldia I, Dotor J, Redrado M, et al. Co-migration of colon cancer cells and CAFs induced by TGFbeta(1) enhances liver metastasis. Cell Tissue Res, 2015, 359(3): 829-839.
39. Villalba M, Evans SR, Vidal-Vanaclocha F, et al. Role of TGF-beta in metastatic colon cancer: it is finally time for targeted therapy. Cell Tissue Res, 2017, 370(1): 29-39.
40. Calon A, Tauriello DV, Batlle E. TGF-βin CAF-mediated tumor growth and metastasis. Semin Cancer Biol, 2014, 25: 15-22.
41. Cheng D, Zhao S, Tang H, et al. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4. Oncotarget, 2016, 7(29): 45199-45213.
42. Itatani Y, Kawada K, Fujishita T, et al. Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1 ⁺ myeloid cells and facilitate liver metastasis. Gastroenterology, 2013, 145(5): 1064-1075.
43. Stiksma J, Grootendorst DC, van der Linden PW. CA 19-9 As a Marker in Addition to CEA to Monitor Colorectal Cancer. Clin Colorectal Cancer, 2014, 13(4): 239-244.
44. Ilantzis C, Demarte L, Screaton RA, et al. Deregulated expression of the human tumor marker CEA and CEA family member CEACAM6 disrupts tissue architecture and blocks colonocyte differentiation. Neoplasia, 2002, 4(2): 151-163.
45. Lee JH, Lee SW. The roles of carcinoembryonic antigen in liver metastasis and therapeutic approaches. Gastroenterol Res Pract, 2017, 2017: 7521987.
46. Hostetter RB, Augustus LB, Mankarious R, et al. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. J Nati Cancer inst, 1990, 82(5): 380-385.

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Research progress about the molecular mechanism of liver metastasis from colorectal cancer

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