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[1]Noritake J, Watanabe T, Sato K, Wang S, Kaibuchi K. IQGAP1. a key regulator of adhesion and migration. J Cell Sci 118, 2085-2092 (2005)
[2]Briggs MW, Sacks DB. IQGAP proteins are integral components of cytoskeletal regulation. EMBO Rep 4, 571-574 (2003)
[3]Sanchez-Laorden B, Viros A, Marais R. Mind the IQGAP. Cancer Cell 23, 715-717 (2013)
[4]Fukata M, Kuroda S, Fujii K, Nakamura T, Shoji I, Matsuura Y, Okawa K, Iwamatsu A, Kikuchi A, Kaibuchi K. Regulation of cross-linking of actin filament by IQGAP1, a target for Cdc42. J Biol Chem 272, 29579-29583 (1997)
[5]Roy M, Li Z, Sacks DB. IQGAP1 binds ERK2 and modulates its activity. JBiol Chem 2004, 279, 17329-17337.
[6]Roy M, Li Z, Sacks DB. IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Mol Cell Biol 25, 7940-7952 (2005)
[7]Hart MJ, Callow MG, Souza B, Polakis P. IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. EMBO J 15, 2997-3005 (1996)
[8]Ho YD, Joyal JL, Li Z, Sacks DB. IQGAP1 integrates Ca2+/calmodulin and Cdc42 signaling. J Biol Chem 274, 464-470 (1999)
[9]Li Z, Kim SH, Higgins JM, Brenner MB, Sacks DB. IQGAP1 and calmodulin modulate E-cadherin function. J Biol Chem 274, 37885-37892 (1999)
[10]Fukata M, Kuroda S, Nakagawa M, Kawajiri A, Itoh N, Shoji I, Matsuura Y, Yonehara S, Fujisawa H, Kikuchi A, Kaibuchi K. Cdc42 and Rac1 regulate the interaction of IQGAP1 with beta-catenin. J Biol Chem 274, 26044-26050 (1999)
[11]Watanabe T, Wang S, Noritake J, Sato K, Fukata M, Takefuji M, Nakagawa M, Izumi N, Akiyama T, Kaibuchi K. Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration. Dev Cell 7, 871-883 (2004)
[12]Johnson M, Sharma M, Henderson BR. IQGAP1 regulation and roles in cancer. Cell Signal 21, 1471-1478 (2009)
[13]Sugimoto N, Imoto I, Fukuda Y, Kurihara N, Kuroda S, Tanigami A. 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 46, 21-25 (2001)
[14]Nabeshima K, Shimao Y, Inoue T, Koono M. Immunohistochemical analysis of IQGAP1 expression in human colorectal carcinomas: its overexpression in carcinomas and association with invasion fronts. Cancer Lett 176, 101-109 (2002)
[15]Bertucci F, Salas S, Eysteries S, Nasser V, Finetti P, Ginestier C, Charafe-Jauffret E. Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters. Oncogene 23, 1377-1391 (2004)
[16]Sun W, Zhang K, Zhang X, Lei W, Xiao T, Ma J, Guo S, Shao S. Identification of differentially expressed genes in human lung squamous cell carcinoma using suppression subtractive hybridization. Cancer Lett 212, 83-93 (2004)
[17]Balenci L, Clarke ID, Dirks PB, Assard N, Ducray F, Jouvet A, Belin MF, Honnorat J, Baudier J. IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme. Cancer Res 66, 9074-9082 (2006)
[18]Dong P, Nabeshima K, Nishimura N, Kawakami T, Hachisuga T, Kawarabayashi T, Iwasaki H. Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas. Cancer Lett 243, 120-127 (2006)
[19]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 7, 23 (2009)
[20]Yamazoe S, Tanaka H, Sawada T, Amano R, Yamada N. RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells. J Exp Clin Cancer Res 29, 53(2010)
[21]Hu J, Verkman AS. Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. FASEB J 20, 1892-1894 (2006)
[22]Noritake J, Fukata M, Sato K, Nakagawa M, Watanabe T. Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact. Mol Biol Cell 15, 1065-1076 (2004)
[23]Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer 2, 133-142 (2002)
[24]White CD, Brown MD, Sacks DB. IQGAPs in cancer: a family of scaffold proteins underlying tumorigenesis. FEBS Lett 583, 1817-1824 (2009)
[25]Wang XX, Li XZ, Zhai LQ, Liu ZR, Chen XJ, Pei Y. Overexpression of IQGAP1 in human pancreatic cancer. Hepatobiliary Pancreat Dis Int 12, 540-545 (2013)
[26]Schmidt VA, Chiariello CS, Capilla E, Miller F, Bahou WF. Development of hepatocellular carcinoma in Iqgap2-deficient mice is IQGAP1 dependent. Mol Cell Biol 28, 1489-1502 (2008)
[27]Zeng H, Yu H, Lu L, Jain D, Kidd MS, Saif MW. Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas 40, 657-663 (2011)
[28]Jameson KL, Mazur PK, Zehnder AM, Zhang J. IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nat Med 19, 626-630 (2013)
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Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Potential involvement of IQGAP1 in proliferation and metastasis of human pancreatic cancer
1 Pathology Center, Shanghai First People’s Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Number 100, Hai-Ning Road, 200080, Shanghai, China
2 Department of Emergency, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, China
Abstract
IQGAP1, as a scaffold protein, integrates diverse cellular functions, including rearrangement of the actin cytoskeleton, cell adhesion, gene transcription and cell cycle regulation. IQGAP1 is elevated in a number of human cancer cells. However little is known about the expression of IQGAP in human pancreatic cancer and its association with cancer proliferation or metastasis. In the present study, we examined the expression of IQGAP1 in different pancreatic cancer cell lines and we found that IQGAP1 level is highly correlated with the degree of malignancy of pancreatic cancer cell metastasis. The proliferation, metastasis, motility and tumorigenesis in SW1990 human pancreatic cells were greatly impaired by down-regulating IQGAP1 expression with RNA interference. Mechanistic analysis indicated that Cdc42/Rac1 pathway might contribute to IQGAP1-mediated-pancreatic cell proliferation and tumorigenesis.
Keywords
- Pancreatic Cancer
- IQGAPs
- ERK2
- APC
References
- [1] Noritake J, Watanabe T, Sato K, Wang S, Kaibuchi K. IQGAP1. a key regulator of adhesion and migration. J Cell Sci 118, 2085-2092 (2005)
- [2] Briggs MW, Sacks DB. IQGAP proteins are integral components of cytoskeletal regulation. EMBO Rep 4, 571-574 (2003)
- [3] Sanchez-Laorden B, Viros A, Marais R. Mind the IQGAP. Cancer Cell 23, 715-717 (2013)
- [4] Fukata M, Kuroda S, Fujii K, Nakamura T, Shoji I, Matsuura Y, Okawa K, Iwamatsu A, Kikuchi A, Kaibuchi K. Regulation of cross-linking of actin filament by IQGAP1, a target for Cdc42. J Biol Chem 272, 29579-29583 (1997)
- [5] Roy M, Li Z, Sacks DB. IQGAP1 binds ERK2 and modulates its activity. JBiol Chem 2004, 279, 17329-17337.
- [6] Roy M, Li Z, Sacks DB. IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Mol Cell Biol 25, 7940-7952 (2005)
- [7] Hart MJ, Callow MG, Souza B, Polakis P. IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. EMBO J 15, 2997-3005 (1996)
- [8] Ho YD, Joyal JL, Li Z, Sacks DB. IQGAP1 integrates Ca2+/calmodulin and Cdc42 signaling. J Biol Chem 274, 464-470 (1999)
- [9] Li Z, Kim SH, Higgins JM, Brenner MB, Sacks DB. IQGAP1 and calmodulin modulate E-cadherin function. J Biol Chem 274, 37885-37892 (1999)
- [10] Fukata M, Kuroda S, Nakagawa M, Kawajiri A, Itoh N, Shoji I, Matsuura Y, Yonehara S, Fujisawa H, Kikuchi A, Kaibuchi K. Cdc42 and Rac1 regulate the interaction of IQGAP1 with beta-catenin. J Biol Chem 274, 26044-26050 (1999)
- [11] Watanabe T, Wang S, Noritake J, Sato K, Fukata M, Takefuji M, Nakagawa M, Izumi N, Akiyama T, Kaibuchi K. Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration. Dev Cell 7, 871-883 (2004)
- [12] Johnson M, Sharma M, Henderson BR. IQGAP1 regulation and roles in cancer. Cell Signal 21, 1471-1478 (2009)
- [13] Sugimoto N, Imoto I, Fukuda Y, Kurihara N, Kuroda S, Tanigami A. 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 46, 21-25 (2001)
- [14] Nabeshima K, Shimao Y, Inoue T, Koono M. Immunohistochemical analysis of IQGAP1 expression in human colorectal carcinomas: its overexpression in carcinomas and association with invasion fronts. Cancer Lett 176, 101-109 (2002)
- [15] Bertucci F, Salas S, Eysteries S, Nasser V, Finetti P, Ginestier C, Charafe-Jauffret E. Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters. Oncogene 23, 1377-1391 (2004)
- [16] Sun W, Zhang K, Zhang X, Lei W, Xiao T, Ma J, Guo S, Shao S. Identification of differentially expressed genes in human lung squamous cell carcinoma using suppression subtractive hybridization. Cancer Lett 212, 83-93 (2004)
- [17] Balenci L, Clarke ID, Dirks PB, Assard N, Ducray F, Jouvet A, Belin MF, Honnorat J, Baudier J. IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme. Cancer Res 66, 9074-9082 (2006)
- [18] Dong P, Nabeshima K, Nishimura N, Kawakami T, Hachisuga T, Kawarabayashi T, Iwasaki H. Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas. Cancer Lett 243, 120-127 (2006)
- [19] 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 7, 23 (2009)
- [20] Yamazoe S, Tanaka H, Sawada T, Amano R, Yamada N. RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells. J Exp Clin Cancer Res 29, 53(2010)
- [21] Hu J, Verkman AS. Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. FASEB J 20, 1892-1894 (2006)
- [22] Noritake J, Fukata M, Sato K, Nakagawa M, Watanabe T. Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact. Mol Biol Cell 15, 1065-1076 (2004)
- [23] Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer 2, 133-142 (2002)
- [24] White CD, Brown MD, Sacks DB. IQGAPs in cancer: a family of scaffold proteins underlying tumorigenesis. FEBS Lett 583, 1817-1824 (2009)
- [25] Wang XX, Li XZ, Zhai LQ, Liu ZR, Chen XJ, Pei Y. Overexpression of IQGAP1 in human pancreatic cancer. Hepatobiliary Pancreat Dis Int 12, 540-545 (2013)
- [26] Schmidt VA, Chiariello CS, Capilla E, Miller F, Bahou WF. Development of hepatocellular carcinoma in Iqgap2-deficient mice is IQGAP1 dependent. Mol Cell Biol 28, 1489-1502 (2008)
- [27] Zeng H, Yu H, Lu L, Jain D, Kidd MS, Saif MW. Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas 40, 657-663 (2011)
- [28] Jameson KL, Mazur PK, Zehnder AM, Zhang J. IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nat Med 19, 626-630 (2013)