BIOMARKER POTENTIAL OF IQ-DOMAIN GTPASE-ACTIVATING PROTEINS FAMILY PROTEIN IN PANCREATIC CANCER: A MINI REVIEW
Objectives: Our present study was done to understand molecular regulatory mechanisms of IQGAP proteins and their potentials as biomarker in pancreatic cancer.
Methods: In this review, relevant studies were obtained by assessing the PubMed database using the combination of words that included â€œIQGAPâ€ and â€œpancreatic cancerâ€.
Results: There is an increasing evidence showing that the expression of IQGAP1 and IQGAP3 is positively correlated with tumorigenesis; however, IQGAP2 might play a role to suppress tumor progression.
Conclusion: IQGAP proteins might have potentials as predictive and prognostic biomarker for human pancreatic cancer.
2. Pelosi E, Castelli G, Testa U. Pancreatic cancer: Molecular characterization, clonal evolution and cancer stem cells. Biomedicines 2017;5: pii: E65.
3. Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer 2002;2:897-909.
4. Pourhoseingholi MA, Ashtari S, Hajizadeh N, Fazeli Z, Zali MR. Systematic review of pancreatic cancer epidemiology in asia-pacific region: Major patterns in GLOBACON 2012. Gastroenterol Hepatol Bed Bench 2017;10:245-57.
5. Ahrendt SA, Pitt HA. Surgical management of pancreatic cancer. Oncology (Williston Park) 2002;16:725-34.
6. Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut 2007;56:1134-52.
7. Fukushige S, Horii A. Road to early detection of pancreatic cancer: Attempts to utilize epigenetic biomarkers. Cancer Lett 2014;342:231-7.
8. Amanam I, Chung V. Targeted therapies for pancreatic cancer. Cancers (Basel) 2018;10: pii: E36.
9. Ishii H, Furuse J, Nagase M, Yoshino M. Impact of gemcitabine on the treatment of metastatic pancreatic cancer. J Gastroenterol Hepatol 2005;20:62-6.
10. Kelley RK, Ko AH. Erlotinib in the treatment of advanced pancreatic cancer. Biologics 2008;2:83-95.
11. Smith JM, Hedman AC, Sacks DB. IQGAPs choreograph cellular signaling from the membrane to the nucleus. Trends Cell Biol 2015;25:171-84.
12. Briggs MW, Sacks DB. IQGAP proteins are integral components of cytoskeletal regulation. EMBO Rep 2003;4:571-4.
13. White CD, Brown MD, Sacks DB. IQGAPs in cancer: A family of scaffold proteins underlying tumorigenesis. FEBS Lett 2009;583:1817 24.
14. Johnson M, Sharma M, Henderson BR. IQGAP1 regulation and roles in cancer. Cell Signal 2009;21:1471-8.
15. Weissbach L, Settleman J, Kalady MF, Snijders AJ, Murthy AE, Yan YX, et al. Identification of a human rasGAP-related protein containing calmodulin-binding motifs. J Biol Chem 1994;269:20517 21.
16. Brill S, Li S, Lyman CW, Church DM, Wasmuth JJ, Weissbach L, et al. The ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and rho family GTPases. Mol Cell Biol 1996;16:4869-78.
17. Wang S, Watanabe T, Noritake J, Fukata M, Yoshimura T, Itoh N, et al. IQGAP3, a novel effector of rac1 and cdc42, regulates neurite outgrowth. J Cell Sci 2007;120:567-77.
18. Huang L, Xu S, Hu D, Lu W, Xie X, Cheng X, et al. IQGAP1 is involved in enhanced aggressive behavior of epithelial ovarian cancer stem cell-like cells during differentiation. Int J Gynecol Cancer 2015;25:559-65.
19. Jin SH, Akiyama Y, Fukamachi H, Yanagihara K, Akashi T, Yuasa Y, et al. IQGAP2 inactivation through aberrant promoter methylation and promotion of invasion in gastric cancer cells. Int J Cancer 2008;122:1040-6.
20. Wang XX, Wang K, Li XZ, Zhai LQ, Qu CX, Zhao Y, et al. Targeted knockdown of IQGAP1 inhibits the progression of esophageal squamous cell carcinoma in vitro and in vivo. PLoS One 2014;9:e96501.
21. Schmidt VA, Chiariello CS, Capilla E, Miller F, Bahou WF. Development of hepatocellular carcinoma in iqgap2-deficient mice is IQGAP1 dependent. Mol Cell Biol 2008;28:1489-502.
22. Xia FD, Wang ZL, Chen HX, Huang Y, Li JD, Wang ZM, et al. Differential expression of IQGAP1/2 in hepatocellular carcinoma and its relationship with clinical outcomes. Asian Pac J Cancer Prev 2014;15:4951-6.
23. White CD, Khurana H, Gnatenko DV, Li Z, Odze RD, Sacks DB, et al. IQGAP1 and IQGAP2 are reciprocally altered in hepatocellular carcinoma. BMC Gastroenterol 2010;10:125.
24. Kunimoto K, Nojima H, Yamazaki Y, Yoshikawa T, Okanoue T, Tsukita S, et al. Involvement of IQGAP3, a regulator of ras/ERK-related cascade, in hepatocyte proliferation in mouse liver regeneration and development. J Cell Physiol 2009;220:621-31.
25. Chen F, Zhu HH, Zhou LF, Wu SS, Wang J, Chen Z, et al. IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by akt activation. Exp Mol Med 2010;42:477-83.
26. Holck S, Nielsen HJ, Hammer E, Christensen IJ, Larsson LI. IQGAP1 in rectal adenocarcinomas: Localization and protein expression before and after radiochemotherapy. Cancer Lett 2015;356:556-60.
27. White CD, Li Z, Dillon DA, Sacks DB. IQGAP1 protein binds human epidermal growth factor receptor 2 (HER2) and modulates trastuzumab resistance. J Biol Chem 2011;286:29734-47.
28. Xie Y, Yan J, Cutz JC, Rybak AP, He L, Wei F, et al. IQGAP2, A candidate tumour suppressor of prostate tumorigenesis. Biochim Biophys Acta 2012;1822:875-84.
29. Wang XX, Li XZ, Zhai LQ, Liu ZR, Chen XJ, Pei Y, et al. Overexpression of IQGAP1 in human pancreatic cancer. Hepatobiliary Pancreat Dis Int 2013;12:540-5.
30. Xu W, Xu B, Yao Y, Yu X, Cao H, Zhang J, et al. Overexpression and biological function of IQGAP3 in human pancreatic cancer. Am J Transl Res 2016;8:5421-32.
31. Matsunaga H, Kubota K, Inoue T, Isono F, Ando O. IQGAP1 selectively interacts with K-ras but not with H-ras and modulates K-ras function. Biochem Biophys Res Commun 2014;444:360-4.
32. Jin Y, Lv X, Zhou J, Chen J. Potential involvement of IQGAP1 in proliferation and metastasis of human pancreatic cancer. Front Biosci (Landmark Ed) 2016;21:1076-83.
33. Jin X, Pan Y, Wang L, Ma T, Zhang L, Tang AH, et al. Fructose-1,6- bisphosphatase inhibits ERK activation and bypasses gemcitabine resistance in pancreatic cancer by blocking IQGAP1-MAPK interaction. Cancer Res 2017;77:4328-41.
34. Hofer MD, Menke A, Genze F, Gierschik P, Giehl K. Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells. Br J Cancer 2004;90:455-62.
35. Osman MA, Sarkar FH, Rodriguez-Boulan E. A molecular rheostat at the interface of cancer and diabetes. Biochim Biophys Acta 2013;1836:166-76.
36. Hage B, Meinel K, Baum I, Giehl K, Menke A. Rac1 activation inhibits E-cadherin-mediated adherens junctions via binding to IQGAP1 in pancreatic carcinoma cells. Cell Commun Signal 2009;7:23.
37. Zeng H, Yu H, Lu L, Jain D, Kidd MS, Saif MW, et al. Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas 2011;40:657-63.
38. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74.
39. Noritake J, Watanabe T, Sato K, Wang S, Kaibuchi K. IQGAP1: A key regulator of adhesion and migration. J Cell Sci 2005;118:2085-92.
40. Wehrle-Haller B. Assembly and disassembly of cell matrix adhesions. Curr Opin Cell Biol 2012;24:569-81.
41. Kimura T, Yamaoka M, Taniguchi S, Okamoto M, Takei M, Ando T, et al. Activated cdc42-bound IQGAP1 determines the cellular endocytic site. Mol Cell Biol 2013;33:4834-43.
42. Roy M, Li Z, Sacks DB. IQGAP1 binds ERK2 and modulates its activity. J Biol Chem 2004;279:17329-37.
43. Roy M, Li Z, Sacks DB. IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Mol Cell Biol 2005;25:7940-52.
44. Ren JG, Li Z, Sacks DB. IQGAP1 integrates ca2+/calmodulin and B-raf signaling. J Biol Chem 2008;283:22972-82.
45. Ren JG, Li Z, Sacks DB. IQGAP1 modulates activation of B-raf. Proc Natl Acad Sci U S A 2007;104:10465-9.
46. SbroggiÃ² M, Carnevale D, Bertero A, Cifelli G, De Blasio E, Mascio G, et al. IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload. Cardiovasc Res 2011;91:456-64.
47. Yamaoka-Tojo M, Ushio-Fukai M, Hilenski L, Dikalov SI, Chen YE, Tojo T, et al. IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species-dependent endothelial migration and proliferation. Circ Res 2004;95:276-83.
48. McNulty DE, Li Z, White CD, Sacks DB, Annan RS. MAPK scaffold IQGAP1 binds the EGF receptor and modulates its activation. J Biol Chem 2011;286:15010-21.
49. Kohno T, Urao N, Ashino T, Sudhahar V, Inomata H, Yamaoka-Tojo M, et al. IQGAP1 links PDGF receptor-Î² signal to focal adhesions involved in vascular smooth muscle cell migration: Role in neointimal formation after vascular injury. Am J Physiol Cell Physiol 2013;305:C591-600.
50. Liu C, Billadeau DD, Abdelhakim H, Leof E, Kaibuchi K, Bernabeu C, et al. IQGAP1 suppresses tÎ²RII-mediated myofibroblastic activation and metastatic growth in liver. J Clin Invest 2013;123:1138-56.
51. Feigin ME, Xue B, Hammell MC, Muthuswamy SK. G-protein-coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion. Proc Natl Acad Sci U S A 2014;111:4191-6.
52. Neel NF, Sai J, Ham AJ, Sobolik-Delmaire T, Mernaugh RL, Richmond A, et al. IQGAP1 is a novel CXCR2-interacting protein and essential component of the â€œchemosynapseâ€. PLoS One 2011;6:e23813.
53. Goto T, Sato A, Shimizu M, Adachi S, Satoh K, Iemura S, et al. IQGAP1 functions as a modulator of dishevelled nuclear localization in wnt signaling. PLoS One 2013;8:e60865.
54. Carmon KS, Gong X, Yi J, Thomas A, Liu Q. RSPO-LGR4 functions via IQGAP1 to potentiate wnt signaling. Proc Natl Acad Sci U S A 2014;111:E1221-9.
55. Nojima H, Adachi M, Matsui T, Okawa K, Tsukita S, Tsukita S, et al. IQGAP3 regulates cell proliferation through the ras/ERK signalling cascade. Nat Cell Biol 2008;10:971-8.
56. Schmidt VA, Scudder L, Devoe CE, Bernards A, Cupit LD, Bahou WF, et al. IQGAP2 functions as a GTP-dependent effector protein in thrombin-induced platelet cytoskeletal reorganization. Blood 2003;101:3021-8.