Functional Mechanisms for Human Tumor Suppressors

Overview

Journal J Cancer

Specialty Oncology

Date 2010 Oct 6

PMID 20922055

Citations 43

Authors

Wanpeng Sun

Jian Yang

Affiliations

Soon will be listed here.

Abstract

Tumor suppressors refer to a large group of molecules that are capable of controlling cell division, promoting apoptosis, and suppressing metastasis. The loss of function for a tumor suppressor may lead to cancer due to uncontrolled cell division. Because of their importance, extensive studies have been undertaken to understand the different functional mechanisms of tumor suppressors. Here, we briefly review the four major mechanisms, inhibition of cell division, induction of apoptosis, DNA damage repair, and inhibition of metastasis. It is noteworthy that some tumor suppressors, such as p53, may adopt more than one mechanism for their functions.

Citing Articles

Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers: a potential novel target?.

Sokolova V, Gruber R, Pammer L, Kocher F, Klieser E, Amann A Mol Biol Rep. 2024; 52(1):87.

PMID: 39729162 PMC: 11680630. DOI: 10.1007/s11033-024-10169-5.

Tumors Established in a Defective Immune Environment Reprogram the Oncogenic Signaling Pathways to Escalate Tumor Antigenicity.

Ke C, Wu H, Wang Y, Huang W, Lin C Biomedicines. 2024; 12(4).

PMID: 38672200 PMC: 11047836. DOI: 10.3390/biomedicines12040846.

Advancements in elucidating the pathogenesis of actinic keratosis: present state and future prospects.

Wang Z, Wang X, Shi Y, Wu S, Ding Y, Yao G Front Med (Lausanne). 2024; 11:1330491.

PMID: 38566927 PMC: 10985158. DOI: 10.3389/fmed.2024.1330491.

Haploinsufficiency of Adenomatous Polyposis Coli Coupled with Kirsten Rat Sarcoma Viral Oncogene Homologue Activation and P53 Loss Provokes High-Grade Glioblastoma Formation in Mice.

Fang K, Su C, Layos J, Lau N, Cheng K Cancers (Basel). 2024; 16(5).

PMID: 38473403 PMC: 10930734. DOI: 10.3390/cancers16051046.

Contribution of Autophagy to Epithelial Mesenchymal Transition Induction during Cancer Progression.

Strippoli R, Niayesh-Mehr R, Adelipour M, Khosravi A, Cordani M, Zarrabi A Cancers (Basel). 2024; 16(4).

PMID: 38398197 PMC: 10886827. DOI: 10.3390/cancers16040807.

References

Weller M, Kleihues P, Dichgans J, Ohgaki H . CD95 ligand: lethal weapon against malignant glioma?. Brain Pathol. 1998; 8(2):285-93. PMC: 8098168. DOI: 10.1111/j.1750-3639.1998.tb00154.x. View

Meehan W, Samant R, Hopper J, Carrozza M, Shevde L, Workman J . Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription. J Biol Chem. 2003; 279(2):1562-9. DOI: 10.1074/jbc.M307969200. View

Nakanishi K, Taniguchi T, Ranganathan V, New H, Moreau L, Stotsky M . Interaction of FANCD2 and NBS1 in the DNA damage response. Nat Cell Biol. 2002; 4(12):913-20. DOI: 10.1038/ncb879. View

Hannon G, Beach D . p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature. 1994; 371(6494):257-61. DOI: 10.1038/371257a0. View

Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y . A p53-dependent checkpoint pathway prevents rereplication. Mol Cell. 2003; 11(4):997-1008. DOI: 10.1016/s1097-2765(03)00099-6. View

Knudson Jr A . Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971; 68(4):820-3. PMC: 389051. DOI: 10.1073/pnas.68.4.820. View

Chim C, Fung T, Liang R . Disruption of INK4/CDK/Rb cell cycle pathway by gene hypermethylation in multiple myeloma and MGUS. Leukemia. 2003; 17(12):2533-5. DOI: 10.1038/sj.leu.2403133. View

Hojilla C, Mohammed F, Khokha R . Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development. Br J Cancer. 2003; 89(10):1817-21. PMC: 2394437. DOI: 10.1038/sj.bjc.6601327. View

Muller H, Helin K . The E2F transcription factors: key regulators of cell proliferation. Biochim Biophys Acta. 2000; 1470(1):M1-12. DOI: 10.1016/s0304-419x(99)00030-x. View

10.

Shiloh Y . ATM (ataxia telangiectasia mutated): expanding roles in the DNA damage response and cellular homeostasis. Biochem Soc Trans. 2001; 29(Pt 6):661-6. DOI: 10.1042/0300-5127:0290661. View

11.

Sherr C, Weber J . The ARF/p53 pathway. Curr Opin Genet Dev. 2000; 10(1):94-9. DOI: 10.1016/s0959-437x(99)00038-6. View

12.

Bertwistle D, Sugimoto M, Sherr C . Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Mol Cell Biol. 2004; 24(3):985-96. PMC: 321449. DOI: 10.1128/MCB.24.3.985-996.2004. View

13.

Fromme J, Banerjee A, Verdine G . DNA glycosylase recognition and catalysis. Curr Opin Struct Biol. 2004; 14(1):43-9. DOI: 10.1016/j.sbi.2004.01.003. View

14.

Sved J, Bird A . The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model. Proc Natl Acad Sci U S A. 1990; 87(12):4692-6. PMC: 54183. DOI: 10.1073/pnas.87.12.4692. View

15.

Komada Y, Zhou Y, Zhang X, Chen T, Tanaka S, Azuma E . Fas/APO-1 (CD95)-mediated cytotoxicity is responsible for the apoptotic cell death of leukaemic cells induced by interleukin-2-activated T cells. Br J Haematol. 1997; 96(1):147-57. DOI: 10.1046/j.1365-2141.1997.8742505.x. View

16.

Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden J, Le Poul E . The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001; 276(37):34631-6. DOI: 10.1074/jbc.M104847200. View

17.

Vandel L, Nicolas E, Vaute O, Ferreira R, Ait-Si-Ali S, Trouche D . Transcriptional repression by the retinoblastoma protein through the recruitment of a histone methyltransferase. Mol Cell Biol. 2001; 21(19):6484-94. PMC: 99795. DOI: 10.1128/MCB.21.19.6484-6494.2001. View

18.

Green R, Wollman R, Kaplan K . APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment. Mol Biol Cell. 2005; 16(10):4609-22. PMC: 1237068. DOI: 10.1091/mbc.e05-03-0259. View

19.

Dong J, Lamb P, Rinker-Schaeffer C, Vukanovic J, Ichikawa T, Isaacs J . KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science. 1995; 268(5212):884-6. DOI: 10.1126/science.7754374. View

20.

He L, Yu J, Liu L, Buyse I, Wang M, Yang Q . RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis. Cancer Res. 1998; 58(19):4238-44. View