A β-catenin/IQGAP1 regulatory feedback loop and its effects on the proliferation of colon cancer cells_Journal of Biomedical Engineering

Authors：

XU Huanji ^1,2 , XIA Hongwei ² , TANG Qiulin ² ,  BI Feng ^1,2

1. Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;
2. Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

BI Feng, Email: bifeng@medmail.com.cn

Keywords：

β-catenin; IQ motif containing GTPase activating protein 1; mitogen-activated protein kinase signaling; cell proliferation

DOI：

10.7507/1001-5515.201701041

Video：

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Abstract Full text Figures/Tables Video References Cited by

The aim of this article is to study the regulatory feedback loop between β-catenin and IQ motif containing GTPase activating protein 1 (IQGAP1), as well as the effect of this regulation loop in colon cancer cell proliferation. Western blot was used to detect the expression of IQGAP1 and β-catenin after changing their expression respectively by transfection in SW1116 cells. CCK-8 cell proliferation assay was used to detect the effect of IQGAP1 involved in the proliferation of SW1116 cells promoted by β-catenin. The results of Western blot indicated that β-catenin could positively regulate IQGAP1, while IQGAP1 silencing could up-regulate β-catenin, forming a negative feedback loop. The results of CCK-8 showed that IQGAP1 silencing inhibited β-catenin-mediated proliferation in SW1116 cells. In conclusion, our research reveals a negative regulatory feedback loop between β-catenin and IQGAP1 which has a remarkable effect on the proliferation ability of colon cancer cells.

Citation： XU Huanji, XIA Hongwei, TANG Qiulin, BI Feng. A β-catenin/IQGAP1 regulatory feedback loop and its effects on the proliferation of colon cancer cells. Journal of Biomedical Engineering, 2018, 35(1): 81-86. doi: 10.7507/1001-5515.201701041 Copy

1.	Chen Wanqing, Zheng Rongshou, Baade P D, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2.	Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell, 2012, 149(6): 1192-1205.
3.	Segditsas S, Tomlinson I. Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene, 2006, 25(57): 7531-7537.
4.	Abel A M, Schuldt K M, Rajasekaran K, et al. IQGAP1: Insights into the function of a molecular puppeteer. Mol Immunol, 2015, 65(2): 336-349.
5.	Smith J M, Hedman A C, Sacks D B. IQGAPs choreograph cellular signaling from the membrane to the nucleus. Trends Cell Biol, 2015, 25(3): 171-184.
6.	Roy M, Li Zhigang, Sacks D B. IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Mol Cell Biol, 2005, 25(18): 7940-7952.
7.	McNulty D E, Li Zhigang, White C D, et al. MAPK scaffold IQGAP1 binds the EGF receptor and modulates its activation. J Biol Chem, 2011, 286(17): 15010-15021.
8.	Jameson K L, Mazur P K, Zehnder A M, et al. IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nat Med, 2013, 19(5): 626-630.
9.	Angers S, Moon R T. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol, 2009, 10(7): 468-477.
10.	Valenta T, Hausmann G, Basler K. The many faces and functions of beta-catenin. EMBO J, 2012, 31(12): 2714-2736.
11.	Niehrs C. The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol, 2012, 13(12): 767-779.
12.	MacDonald B T, Tamai K, He Xi. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell, 2009, 17(1): 9-26.
13.	Rodriguez-Salas N, Dominguez G, Barderas R, et al. Clinical relevance of colorectal cancer molecular subtypes. Crit Rev Oncol Hematol, 2017, 109: 9-19.
14.	Noritake J, Watanabe T, Sato K, et al. IQGAP1: a key regulator of adhesion and migration. J Cell Sci, 2005, 118(Pt 10): 2085-2092.
15.	Sugimoto N, Imoto I, Fukuda Y, et al. IQGAP1, a negative regulator of cell-cell adhesion, is upregulated by gene amplification at 15q26 in gastric cancer cell lines HSC39 and 40A. J Hum Genet, 2001, 46(1): 21-25.
16.	Fukuda Y, Kurihara N, Imoto I, et al. CD44 is a potential target of amplification within the 11p13 amplicon detected in gastric cancer cell lines. Genes Chromosomes Cancer, 2000, 29(4): 315-324.
17.	Roy M, Li Zhigang, Sacks D B. IQGAP1 binds ERK2 and modulates its activity. J Biol Chem, 2004, 279(17): 17329-17337.
18.	Ren J G, Li Zhigang, Sacks D B. IQGAP1 modulates activation of B-Raf. Proc Natl Acad Sci U S A, 2007, 104(25): 10465-10469.
19.	Matsunaga H, Kubota K, Inoue T, et al. IQGAP1 selectively interacts with K-Ras but not with H-Ras and modulates K-Ras function. Biochem Biophys Res Commun, 2014, 444(3): 360-364.
20.	Amaro A, Chiara S, Pfeffer U. Molecular evolution of colorectal cancer: from multistep carcinogenesis to the big bang. Cancer Metastasis Rev, 2016, 35(1): 63-74.
21.	Bikkavilli R K, Malbon C C. Mitogen-activated protein kinases and Wnt/beta-catenin signaling: Molecular conversations among signaling pathways. Commun Integr Biol, 2009, 2(1): 46-49.
22.	Guturi K K, Mandal T, Chatterjee A, et al. Mechanism of beta-catenin-mediated Transcriptional regulation of epidermal growth factor receptor expression in glycogen synthase kinase 3 beta-inactivated prostate cancer cells. J Biol Chem, 2012, 287(22): 18287-18296.
23.	Latasa M U, Salis F, Urtasun R, et al. Regulation of amphiregulin gene expression by beta-catenin signaling in human hepatocellular carcinoma cells: a novel crosstalk between FGF19 and the EGFR system. PLoS One, 2012, 7(12): e52711.
24.	Ding Qingqing, Xia Weiya, Liu J C, et al. Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin. Mol Cell, 2005, 19(2): 159-170.
25.	Jin Xuewen, Liu Yuling, Liu Jingjing, et al. The overexpression of IQGAP1 and β-catenin is associated with tumor progression in hepatocellular carcinoma in vitro and in vivo. PLoS One, 2015, 10(8): e0133770.
26.	Masuda M, Sawa M, Yamada T. Therapeutic targets in the Wnt signaling pathway: Feasibility of targeting TNIK in colorectal cancer. Pharmacol Ther, 2015, 156: 1-9.

1. Chen Wanqing, Zheng Rongshou, Baade P D, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell, 2012, 149(6): 1192-1205.
3. Segditsas S, Tomlinson I. Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene, 2006, 25(57): 7531-7537.
4. Abel A M, Schuldt K M, Rajasekaran K, et al. IQGAP1: Insights into the function of a molecular puppeteer. Mol Immunol, 2015, 65(2): 336-349.
5. Smith J M, Hedman A C, Sacks D B. IQGAPs choreograph cellular signaling from the membrane to the nucleus. Trends Cell Biol, 2015, 25(3): 171-184.
6. Roy M, Li Zhigang, Sacks D B. IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Mol Cell Biol, 2005, 25(18): 7940-7952.
7. McNulty D E, Li Zhigang, White C D, et al. MAPK scaffold IQGAP1 binds the EGF receptor and modulates its activation. J Biol Chem, 2011, 286(17): 15010-15021.
8. Jameson K L, Mazur P K, Zehnder A M, et al. IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nat Med, 2013, 19(5): 626-630.
9. Angers S, Moon R T. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol, 2009, 10(7): 468-477.
10. Valenta T, Hausmann G, Basler K. The many faces and functions of beta-catenin. EMBO J, 2012, 31(12): 2714-2736.
11. Niehrs C. The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol, 2012, 13(12): 767-779.
12. MacDonald B T, Tamai K, He Xi. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell, 2009, 17(1): 9-26.
13. Rodriguez-Salas N, Dominguez G, Barderas R, et al. Clinical relevance of colorectal cancer molecular subtypes. Crit Rev Oncol Hematol, 2017, 109: 9-19.
14. Noritake J, Watanabe T, Sato K, et al. IQGAP1: a key regulator of adhesion and migration. J Cell Sci, 2005, 118(Pt 10): 2085-2092.
15. Sugimoto N, Imoto I, Fukuda Y, et al. IQGAP1, a negative regulator of cell-cell adhesion, is upregulated by gene amplification at 15q26 in gastric cancer cell lines HSC39 and 40A. J Hum Genet, 2001, 46(1): 21-25.
16. Fukuda Y, Kurihara N, Imoto I, et al. CD44 is a potential target of amplification within the 11p13 amplicon detected in gastric cancer cell lines. Genes Chromosomes Cancer, 2000, 29(4): 315-324.
17. Roy M, Li Zhigang, Sacks D B. IQGAP1 binds ERK2 and modulates its activity. J Biol Chem, 2004, 279(17): 17329-17337.
18. Ren J G, Li Zhigang, Sacks D B. IQGAP1 modulates activation of B-Raf. Proc Natl Acad Sci U S A, 2007, 104(25): 10465-10469.
19. Matsunaga H, Kubota K, Inoue T, et al. IQGAP1 selectively interacts with K-Ras but not with H-Ras and modulates K-Ras function. Biochem Biophys Res Commun, 2014, 444(3): 360-364.
20. Amaro A, Chiara S, Pfeffer U. Molecular evolution of colorectal cancer: from multistep carcinogenesis to the big bang. Cancer Metastasis Rev, 2016, 35(1): 63-74.
21. Bikkavilli R K, Malbon C C. Mitogen-activated protein kinases and Wnt/beta-catenin signaling: Molecular conversations among signaling pathways. Commun Integr Biol, 2009, 2(1): 46-49.
22. Guturi K K, Mandal T, Chatterjee A, et al. Mechanism of beta-catenin-mediated Transcriptional regulation of epidermal growth factor receptor expression in glycogen synthase kinase 3 beta-inactivated prostate cancer cells. J Biol Chem, 2012, 287(22): 18287-18296.
23. Latasa M U, Salis F, Urtasun R, et al. Regulation of amphiregulin gene expression by beta-catenin signaling in human hepatocellular carcinoma cells: a novel crosstalk between FGF19 and the EGFR system. PLoS One, 2012, 7(12): e52711.
24. Ding Qingqing, Xia Weiya, Liu J C, et al. Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin. Mol Cell, 2005, 19(2): 159-170.
25. Jin Xuewen, Liu Yuling, Liu Jingjing, et al. The overexpression of IQGAP1 and β-catenin is associated with tumor progression in hepatocellular carcinoma in vitro and in vivo. PLoS One, 2015, 10(8): e0133770.
26. Masuda M, Sawa M, Yamada T. Therapeutic targets in the Wnt signaling pathway: Feasibility of targeting TNIK in colorectal cancer. Pharmacol Ther, 2015, 156: 1-9.

Journal of Biomedical Engineering

A β-catenin/IQGAP1 regulatory feedback loop and its effects on the proliferation of colon cancer cells

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