Mechanisms Regulating Microtubule Binding, DNA Replication, and Apoptosis are Controlled by the Intestinal Tumor Suppressor APC

Current Colorectal Cancer Reports - Tập 7 - Trang 145-151 - 2011
Erin M. Perchiniak1, Joanna Groden1
1Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine, Columbus, USA

Tóm tắt

Colorectal cancer (CRC) results from the progressive accumulation of both genetic and epigenetic alterations that lead to the transformation of normal colorectal epithelium to benign (adenoma) and invasive (carcinoma) disease. Since its discovery in mutated form as the causative gene for familial adenomatous polyposis coli (FAP), as well as in many sporadic CRCs, the APC tumor suppressor has been shown to possess numerous functions within the cell including regulation of WNT signaling pathways and its transcriptional effects, cell migration, and chromosome separation. In recent years, other novel roles for APC have been investigated and suggest that APC can also repress DNA replication and enhance apoptosis. Further insights into the mechanisms by which APC contributes to tumor suppression will accelerate the diagnosis and treatment of CRC.

Tài liệu tham khảo

Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67.

Nishisho I, Nakamura Y, Miyoshi Y, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991;253:665–9.

Groden J, Thliveris A, Samowitz W, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991;66:589–600.

Leppert M, Dobbs M, Scambler P, et al. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987;238:1411–3.

Nathke I. Cytoskeleton out of the cupboard: colon cancer and cytoskeletal changes induced by loss of APC. Nat Rev Cancer. 2006;6:967–74.

Nathke IS. The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Annu Rev Cell Dev Biol. 2004;20:337–66.

Watson SA. Oncogenic targets of beta-catenin-mediated transcription in molecular pathogenesis of intestinal polyposis. Lancet. 2001;357:572–3.

Samowitz WS, Powers MD, Spirio LN, et al. Beta-catenin mutations are more frequent in small colorectal adenomas than in larger adenomas and invasive carcinomas. Cancer Res. 1999;59:1442–4.

Blaker H, Scholten M, Sutter C, et al. Somatic mutations in familial adenomatous polyps. Nuclear translocation of beta-catenin requires more than biallelic APC inactivation. Am J Clin Pathol. 2003;120:418–23.

Anderson CB, Neufeld KL, White RL. Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon. Proc Natl Acad Sci USA. 2002;99:8683–8.

Neufeld KL, White RL. Nuclear and cytoplasmic localizations of the adenomatous polyposis coli protein. Proc Natl Acad Sci USA. 1997;94:3034–9.

Zhang F, White RL, Neufeld KL. Phosphorylation near nuclear localization signal regulates nuclear import of adenomatous polyposis coli protein. Proc Natl Acad Sci USA. 2000;97:12577–82.

Rosin-Arbesfeld R, Townsley F, Bienz M. The APC tumour suppressor has a nuclear export function. Nature. 2000;406:1009–12.

Baeg GH, Matsumine A, Kuroda T, et al. The tumour suppressor gene product APC blocks cell cycle progression from G0/G1 to S phase. EMBO J. 1995;14:5618–25.

Heinen CD, Goss KH, Cornelius JR, et al. The APC tumor suppressor controls entry into S-phase through its ability to regulate the cyclin D/RB pathway. Gastroenterology. 2002;123:751–63.

Carson DJ, Santoro IM, Groden J. Isoforms of the APC tumor suppressor and their ability to inhibit cell growth and tumorigenicity. Oncogene. 2004;23:7144–8.

Sierra J, Yoshida T, Joazeiro CA, Jones KA. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev. 2006;20:586–600.

Deka J, Herter P, Sprenger-Haussels M, et al. The APC protein binds to A/T rich DNA sequences. Oncogene. 1999;18:5654–61.

Deka J, Kuhlmann J, Muller O. A domain within the tumor suppressor protein APC shows very similar biochemical properties as the microtubule-associated protein tau. Eur J Biochem. 1998;253:591–7.

Zumbrunn J, Kinoshita K, Hyman AA, Nathke IS. Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol. 2001;11:44–9.

Dikovskaya D, Newton IP, Nathke IS. The adenomatous polyposis coli protein is required for the formation of robust spindles formed in CSF Xenopus extracts. Mol Biol Cell. 2004;15:2978–91.

Wen Y, Eng CH, Schmoranzer J, et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol. 2004;6:820–30.

• Murawala P, Tripathi MM, Vyas P, et al. Nup358 interacts with APC and plays a role in cell polarization. J Cell Sci. 2009;122:3113–22. This article presents and discusses experiments to demonstrate that APC is targeted to the plus-ends of MTs by kinesin-2 and the nuclear-cytoplasmic transport protein Nup358.

• Dikovskaya D, Li Z, Newton IP, et al. Microtubule assembly by the Apc protein is regulated by importin-beta-RanGTP. J Cell Sci. 2009;123:736–46. This article presents and discusses experiments to demonstrate that APC directly interacts with importin-β, a transport factor involved in nuclear import, to inhibit the ability of APC to assemble and bundle MTs.

Fodde R, Kuipers J, Rosenberg C, et al. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol. 2001;3:433–8.

Dikovskaya D, Schiffmann D, Newton IP, et al. Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis. J Cell Biol. 2007;176:183–95.

•• Qian J, Sarnaik AA, Bonney TM, et al. The APC tumor suppressor inhibits DNA replication by directly binding to DNA via its carboxyl terminus. Gastroenterology 2008;135:152–62. This article presents and discusses experiments to demonstrate that the carboxy-terminal of APC contains DNA-binding sequences to inhibit DNA replication directly.

Munemitsu S, Souza B, Muller O, et al. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 1994;54:3676–81.

Smith KJ, Levy DB, Maupin P, et al. Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res. 1994;54:3672–5.

Li W, Wang XS, Qu MH, et al. Human protein tau represses DNA replication in vitro. Biochim Biophys Acta. 2005;1726:280–6.

Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell. 1997;88:347–54.

Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.

Kaufmann SH, Hengartner MO. Programmed cell death: alive and well in the new millennium. Trends Cell Biol. 2001;11:526–34.

Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309–12.

Salvesen GS, Dixit VM. Caspase activation: the induced-proximity model. Proc Natl Acad Sci USA. 1999;96:10964–7.

Budihardjo I, Oliver H, Lutter M, et al. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999;15:269–90.

Green DR, Evan GI. A matter of life and death. Cancer Cell. 2002;1:19–30.

Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9:47–59.

Green DR, Chipuk JE. Apoptosis: stabbed in the BAX. Nature. 2008;455:1047–9.

Chipuk JE, Bouchier-Hayes L, Green DR. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ. 2006;13:1396–402.

Bedi A, Pasricha PJ, Akhtar AJ, et al. Inhibition of apoptosis during development of colorectal cancer. Cancer Res. 1995;55:1811–6.

Hall PA, Coates PJ, Ansari B, Hopwood D. Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis. J Cell Sci. 1994;107(Pt 12):3569–77.

Merritt AJ, Potten CS, Watson AJ, et al. Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Sci. 1995;108(Pt 6):2261–71.

Morin PJ, Vogelstein B, Kinzler KW. Apoptosis and APC in colorectal tumorigenesis. Proc Natl Acad Sci USA. 1996;93:7950–4.

Steigerwald K, Behbehani GK, Combs KA, et al. The APC tumor suppressor promotes transcription-independent apoptosis in vitro. Mol Cancer Res. 2005;3:78–89.

Qian J, Steigerwald K, Combs KA, et al. Caspase cleavage of the APC tumor suppressor and release of an amino-terminal domain is required for the transcription-independent function of APC in apoptosis. Oncogene. 2007;26:4872–6.

Webb SJ, Nicholson D, Bubb VJ, Wyllie AH. Caspase-mediated cleavage of APC results in an amino-terminal fragment with an intact armadillo repeat domain. FASEB J. 1999;13:339–46.

Browne SJ, MacFarlane M, Cohen GM, Paraskeva C. The adenomatous polyposis coli protein and retinoblastoma protein are cleaved early in apoptosis and are potential substrates for caspases. Cell Death Differ. 1998;5:206–13.

•• Qian J, Perchiniak EM, Sun K, Groden J: The mitochondrial protein hTID-1 partners with the caspase-cleaved adenomatous polyposis cell tumor suppressor to facilitate apoptosis. Gastroenterology 2010;138:1418–28. This article presents and discusses experiments to demonstrate that caspase cleavage of APC releases an amino-terminal segment that relocates to the mitochondria and interacts with an hTID-1 isoform to promote apoptosis.

Polakis P. The adenomatous polyposis coli (APC) tumor suppressor. Biochim Biophys Acta. 1997;1332:F127–47.

Yin X, Rozakis-Adcock M. Genomic organization and expression of the human tumorous imaginal disc (TID1) gene. Gene. 2001;278:201–10.

Kurzik-Dumke U, Czaja J. Htid-1, the human homolog of the Drosophila melanogaster l(2)tid tumor suppressor, defines a novel physiological role of APC. Cell Signal. 2007;19:1973–85.

Syken J, De-Medina T, Munger K. TID1, a human homolog of the Drosophila tumor suppressor l(2)tid, encodes two mitochondrial modulators of apoptosis with opposing functions. Proc Natl Acad Sci USA. 1999;96:8499–504.

Kurzik-Dumke U, Horner M, Czaja J, et al. Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor. Int J Mol Med. 2008;21:19–31.

•• Brocardo M, Lei Y, Tighe A, et al. Mitochondrial targeting of adenomatous polyposis coli protein is stimulated by truncating cancer mutations: regulation of Bcl-2 and implications for cell survival. J Biol Chem. 2008;283:5950–9. This article presents and discusses experiments to demonstrate that truncated APC interacts with Bcl2 to stabilize Bcl2 at the mitochondria and to promote cell survival.

Schilling B, De-Medina T, Syken J, et al. A novel human DnaJ protein, hTid-1, a homolog of the Drosophila tumor suppressor protein Tid56, can interact with the human papillomavirus type 16 E7 oncoprotein. Virology. 1998;247:74–85.

Trentin GA, Yin X, Tahir S, et al. A mouse homologue of the Drosophila tumor suppressor l(2)tid gene defines a novel Ras GTPase-activating protein (RasGAP)-binding protein. J Biol Chem. 2001;276:13087–95.

Zhang T, Otevrel T, Gao Z, et al. Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Res. 2001;61:8664–7.

Huang X, Guo B. Adenomatous polyposis coli determines sensitivity to histone deacetylase inhibitor-induced apoptosis in colon cancer cells. Cancer Res. 2006;66:9245–51.

Thông tin
Thông tin xuất bản

Current Colorectal Cancer Reports

Tập 7

145-151

Thông tin tác giả