Study on the mechanism of c-Met expression on invasion and metastasis of colorectal cancer by gene microarray_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YAO Jianfeng ¹ , TIAN Lifei ¹ , ZHANG Xiaolong ¹ ,  SUN Xuejun ²

1. First Depatment of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, R. P. China;
2. Depatment of General Surgery, The First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an 710061, R. P. China;

Corresponding author：

SUN Xuejun, Email: sunxy@mail.xjtu.edu.cn

Keywords：

gene chip; c-Met; colorectal cancer; invasion; metastasis

DOI：

10.7507/1007-9424.201908012

Video：

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Objective To study the mechanism of the effect on invasion and metastasis of colorectal cancer by down-regulating c-Met gene.Methods c-Met genes were knocked down in SW480 cells, differential genes were screened by gene chip, functional cluster analysis of differential genes was carried out, and IPA was used to analyze the interaction network of cell signal pathway and related differential genes, as well as the ralationship between related genes and upstream regulatory molecules. The related genes in the suppressed signal pathway were selected for qPCR verification.Results After knockdown of c-Met, the number of up-regulated genes and down-regulated genes in SW480 cells was 399 and 286, respectively. Cluster analysis showed that c-Met knockdown had a great effect on the gene expression level of SW480 cells, IPA pathway analysis showed that HGF signaling pathway was suppressed, and after c-Met knockdown, IPA interaction network suggested that AKT2, PIK3CA, and MAP2K4 in HGF pathway were down-regulated, and qPCR verified that the above genes were also down-regulated, which was consistent with the results of microarray.Conclusion c-Met may affect the invasion and metastasis of colorectal cancer through the regulation of AKT2, PIK3CA, and MAP2K4 in HGF pathway.

Citation： YAO Jianfeng, TIAN Lifei, ZHANG Xiaolong, SUN Xuejun. Study on the mechanism of c-Met expression on invasion and metastasis of colorectal cancer by gene microarray. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(4): 442-447. doi: 10.7507/1007-9424.201908012 Copy

1.	姚建锋, 孙学军, 闫立昆, 等. C-Met 在有、无肝转移结直肠癌组织中的表达差异. 中国普通外科杂志, 2014, 23(4): 468-427.
2.	姚建锋, 孙学军, 闫立昆, 等. C-Met 在结直肠癌细胞株中的表达及其配体肝细胞生长因子对SW480细胞株增殖和侵袭能力的影响. 中国普外基础与临床杂志, 2015, 22(11): 1314-1318.
3.	Arboleda MJ, Lyons JF, Kabbinavar FF, et al. Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells. Cancer Res, 2003, 63(1): 196-206.
4.	Du L, Chen X, Cao Y, et al. Overexpression of PIK3CA in murine head and neck epithelium drives tumor invasion and metastasis through PDK1 and enhanced TGFβ signaling. Oncogene, 2016, 35(35): 4641-4652.
5.	Wang PN, Huang J, Duan YH, et al. Downregulation of phosphorylated MKK4 is associated with a poor prognosis in colorectal cancer patients. Oncotarget, 2017, 8(21): 34352-34361.
6.	Wang Y, Zhang QJ, Wang HS, et al. Genome-wide microarray analysis identifies a potential Role for striatal retrograde endocannabinoid signaling in the pathogenesis of experimental L-DOPA-induced dyskinesia. Synapse, 2014, 68(8): 332-343.
7.	Lenk GM, Tromp G, Weinsheimer S, et al. Whole genome expression profiling reveals a significant role for immune function in human abdominal aortic aneurysms. BMC Genomics, 2007, 8: 237.
8.	Kim JH, Kim HS, Kim BJ, et al. Prognostic value of c-Met overexpression in hepatocellular carcinoma: a meta-analysis and review. Oncotarget, 2017, 8(52): 90351-90357.
9.	Li L, Sun Z, Huang X, et al. Role of c-Met expression on prognosis of head and neck cancer: A literature review and meta-analysis. Head Neck, 2019, 41(6): 1999-2006.
10.	Kim JH, Jang HJ, Kim HS, et al. Prognostic impact of high c-Met expression in ovarian cancer: a meta-analysis. J Cancer, 2018, 9(19): 3427-3434.
11.	Cuneo KC, Morgan MA, Griffith KA, et al. Prognostic value of c-MET expression in patients with pancreatic cancer receiving adjuvant and neoadjuvant chemoradiation therapy. Int J Radiat Oncol Biol Phys, 2018, 100(2): 490-497.
12.	Miao L, Lu Y, Xu Y, et al. PD-L1 and c-MET expression and survival in patients with small cell lung cancer. Oncotarget, 2017, 8(33): 53978-53988.
13.	Pyo JS, Kang G, Cho H. Clinicopathological significance and diagnostic accuracy of c-MET expression by immuno-histochemistry in gastric cancer: a meta-analysis. J Gastric Cancer, 2016, 16(3): 141-151.
14.	Gao H, Guan M, Sun Z, et al. High c-Met expression is a negative prognostic marker for colorectal cancer: a meta-analysis. Tumour Biol, 2015, 36(2): 515-520.
15.	Jacobsen F, Ashtiani SN, Tennstedt P, et al. High c-MET expression is frequent but not associated with early PSA recurrence in prostate cancer. Exp Ther Med, 2013, 5(1): 102-106.
16.	Shali H, Ahmadi M, Kafil HS, et al. IGF1R and c-met as therapeutic targets for colorectal cancer. Biomed Pharmacother, 2016, 82: 528-536.
17.	Bradley CA, Dunne PD, Bingham V, et al. Transcriptional upregulation of c-MET is associated with invasion and tumor budding in colorectal cancer. Oncotarget, 2016, 7(48): 78932-78945.
18.	Ryehahou PG, Kang J, Gulhati P, et al. Akt2 overexprer, sion plap a critical role in the establishment of colorectal cancer metastasis. Proc Natl Acad Sci USA, 2008, 105(51): 20315-20320.
19.	Lim WT, Zhang WH, Miller CR, et al. PTEN and phosphorylated AKT expression and prognosis in early and late stage non small cell lung cancer. Oncol Rep, 2007, 17(4): 853-857.
20.	Maurice-Duelli A, Ndoye A, Bouali S, et al. Enhanced cell growth inhibition following PTEN nonviral gene transfer using polyethylenimine and photochemical internalization in endometrial cancer cells. Technol Cancer Res Treat, 2004, 3(5): 459-466.
21.	Khan S, Kumagai T, Vora J, et al. PTEN promoter is methylated in a proportion of invasive breast cancers. Int J Cancer, 2004, 112(3): 407-408.
22.	Shiratsuchi H, Basson MD. AKT2, but not AKT1 or AKT3 mediates pressure stimulated serum-opsonized latex bead phagocytosis through activating mTOR and p70 S6 kinase. J Cell Biochem, 2007, 102(2): 353367.
23.	Cheng GZ, Zhang W, Wang LH, et al. Regulation of cancer cell survival, migration, and invasion by Twist: AKT2 comes to interplay. Cancer Res, 2008, 68(4): 957-960.
24.	Agarwal E, Robb CM, Smith LM, et al. Role of Akt2 in regulation of metastasis suppressor l expression and colorectal cancer metastasis. Oncogene, 2017, 36(22): 3104-3118.
25.	Ma YY, Wei SJ, Lin YC. PIK3CA as an oncogene in cervical cancer. Oncogene, 2000, 19(23): 2739-2744.
26.	Samuels Y, Diaz LA Jr, Schmidt-Kittler O, et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell, 2005, 7(6): 561-573.
27.	Yarbrough WG, Whigham A, Brown B, et al. Phosphoinositide kinase-3 status associated with presence or absence of human papillomavirus in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys, 2007, 69(2 Suppl): S98-S101.
28.	Pavese JM, Ogden IM, Voll EA, et al. Mitogen-activated protein kinase kinase 4(MAP2K4) promotes human prostate cancer metastasis. PLoS One, 2014, 9(7): e102289.

1. 姚建锋, 孙学军, 闫立昆, 等. C-Met 在有、无肝转移结直肠癌组织中的表达差异. 中国普通外科杂志, 2014, 23(4): 468-427.
2. 姚建锋, 孙学军, 闫立昆, 等. C-Met 在结直肠癌细胞株中的表达及其配体肝细胞生长因子对SW480细胞株增殖和侵袭能力的影响. 中国普外基础与临床杂志, 2015, 22(11): 1314-1318.
3. Arboleda MJ, Lyons JF, Kabbinavar FF, et al. Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells. Cancer Res, 2003, 63(1): 196-206.
4. Du L, Chen X, Cao Y, et al. Overexpression of PIK3CA in murine head and neck epithelium drives tumor invasion and metastasis through PDK1 and enhanced TGFβ signaling. Oncogene, 2016, 35(35): 4641-4652.
5. Wang PN, Huang J, Duan YH, et al. Downregulation of phosphorylated MKK4 is associated with a poor prognosis in colorectal cancer patients. Oncotarget, 2017, 8(21): 34352-34361.
6. Wang Y, Zhang QJ, Wang HS, et al. Genome-wide microarray analysis identifies a potential Role for striatal retrograde endocannabinoid signaling in the pathogenesis of experimental L-DOPA-induced dyskinesia. Synapse, 2014, 68(8): 332-343.
7. Lenk GM, Tromp G, Weinsheimer S, et al. Whole genome expression profiling reveals a significant role for immune function in human abdominal aortic aneurysms. BMC Genomics, 2007, 8: 237.
8. Kim JH, Kim HS, Kim BJ, et al. Prognostic value of c-Met overexpression in hepatocellular carcinoma: a meta-analysis and review. Oncotarget, 2017, 8(52): 90351-90357.
9. Li L, Sun Z, Huang X, et al. Role of c-Met expression on prognosis of head and neck cancer: A literature review and meta-analysis. Head Neck, 2019, 41(6): 1999-2006.
10. Kim JH, Jang HJ, Kim HS, et al. Prognostic impact of high c-Met expression in ovarian cancer: a meta-analysis. J Cancer, 2018, 9(19): 3427-3434.
11. Cuneo KC, Morgan MA, Griffith KA, et al. Prognostic value of c-MET expression in patients with pancreatic cancer receiving adjuvant and neoadjuvant chemoradiation therapy. Int J Radiat Oncol Biol Phys, 2018, 100(2): 490-497.
12. Miao L, Lu Y, Xu Y, et al. PD-L1 and c-MET expression and survival in patients with small cell lung cancer. Oncotarget, 2017, 8(33): 53978-53988.
13. Pyo JS, Kang G, Cho H. Clinicopathological significance and diagnostic accuracy of c-MET expression by immuno-histochemistry in gastric cancer: a meta-analysis. J Gastric Cancer, 2016, 16(3): 141-151.
14. Gao H, Guan M, Sun Z, et al. High c-Met expression is a negative prognostic marker for colorectal cancer: a meta-analysis. Tumour Biol, 2015, 36(2): 515-520.
15. Jacobsen F, Ashtiani SN, Tennstedt P, et al. High c-MET expression is frequent but not associated with early PSA recurrence in prostate cancer. Exp Ther Med, 2013, 5(1): 102-106.
16. Shali H, Ahmadi M, Kafil HS, et al. IGF1R and c-met as therapeutic targets for colorectal cancer. Biomed Pharmacother, 2016, 82: 528-536.
17. Bradley CA, Dunne PD, Bingham V, et al. Transcriptional upregulation of c-MET is associated with invasion and tumor budding in colorectal cancer. Oncotarget, 2016, 7(48): 78932-78945.
18. Ryehahou PG, Kang J, Gulhati P, et al. Akt2 overexprer, sion plap a critical role in the establishment of colorectal cancer metastasis. Proc Natl Acad Sci USA, 2008, 105(51): 20315-20320.
19. Lim WT, Zhang WH, Miller CR, et al. PTEN and phosphorylated AKT expression and prognosis in early and late stage non small cell lung cancer. Oncol Rep, 2007, 17(4): 853-857.
20. Maurice-Duelli A, Ndoye A, Bouali S, et al. Enhanced cell growth inhibition following PTEN nonviral gene transfer using polyethylenimine and photochemical internalization in endometrial cancer cells. Technol Cancer Res Treat, 2004, 3(5): 459-466.
21. Khan S, Kumagai T, Vora J, et al. PTEN promoter is methylated in a proportion of invasive breast cancers. Int J Cancer, 2004, 112(3): 407-408.
22. Shiratsuchi H, Basson MD. AKT2, but not AKT1 or AKT3 mediates pressure stimulated serum-opsonized latex bead phagocytosis through activating mTOR and p70 S6 kinase. J Cell Biochem, 2007, 102(2): 353367.
23. Cheng GZ, Zhang W, Wang LH, et al. Regulation of cancer cell survival, migration, and invasion by Twist: AKT2 comes to interplay. Cancer Res, 2008, 68(4): 957-960.
24. Agarwal E, Robb CM, Smith LM, et al. Role of Akt2 in regulation of metastasis suppressor l expression and colorectal cancer metastasis. Oncogene, 2017, 36(22): 3104-3118.
25. Ma YY, Wei SJ, Lin YC. PIK3CA as an oncogene in cervical cancer. Oncogene, 2000, 19(23): 2739-2744.
26. Samuels Y, Diaz LA Jr, Schmidt-Kittler O, et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell, 2005, 7(6): 561-573.
27. Yarbrough WG, Whigham A, Brown B, et al. Phosphoinositide kinase-3 status associated with presence or absence of human papillomavirus in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys, 2007, 69(2 Suppl): S98-S101.
28. Pavese JM, Ogden IM, Voll EA, et al. Mitogen-activated protein kinase kinase 4(MAP2K4) promotes human prostate cancer metastasis. PLoS One, 2014, 9(7): e102289.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study on the mechanism of c-Met expression on invasion and metastasis of colorectal cancer by gene microarray

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