The Key Role of Telomerase in The Initiation and Treatment of Colon Cancer: New Advances and Prospects
Main Article Content
Abstract
Telomeres are important regions for maintaining genome stability, and their dysfunction is closely related to the occurrence of colon cancer. This article reviews the recent progress in the study of telomeres and telomerase in colon cancer, and highlights the key role of telomerase in inducing telomere dysfunction and immortalization of cancer cells. Modulating telomerase activity has become a potential strategy to inhibit the proliferation of cancer cells, including immunotherapy, telomerase inhibitors and TERT gene targeted therapy, which provides prospects for the treatment of colon cancer. Finally, recommendations are made regarding the development of therapeutic strategies targeting telomerase.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
SIEGEL R L, MILLER K D, FUCHS H E, et al.Cancer statistics, 2022[J].CA: a Cancer Journal For Clinicians,2022, 72 (1).
WU C, LI M, MENG H, et al.Analysis of status and countermeasures of cancer incidence and mortality in China[J].Science China. Life Sciences,2019, 62 (5): 640-647.
FENG R-M, ZONG Y-N, CAO S-M, et al.Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?[J].Cancer Communications (London, England),2019, 39 (1): 22.
XIA C, DONG X, LI H, et al.Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J].Chinese Medical Journal,2022, 135 (5): 584-590.
MILLER K D, NOGUEIRA L, DEVASIA T, et al.Cancer treatment and survivorship statistics, 2022[J].CA: a Cancer Journal For Clinicians,2022, 72 (5): 409-436.
VICTORELLI S, PASSOS J F.Telomeres and Cell Senescence - Size Matters Not[J].EBioMedicine,2017, 21: 14-20.
NEIDLE S, PARKINSON G.Telomere maintenance as a target for anticancer drug discovery[J].Nature Reviews. Drug Discovery,2002, 1 (5): 383-393.
LENGAUER C, KINZLER K W, VOGELSTEIN B.Genetic instabilities in human cancers[J].Nature,1998, 396 (6712): 643- 649.
MIZUKOSHI E, KANEKO S.Telomerase-Targeted Cancer Immunotherapy[J].International Journal of Molecular Sciences,2019, 20 (8).
GUTERRES A N, VILLANUEVA J.Targeting telomerase for cancer therapy[J].Oncogene,2020, 39 (36): 5811-5824.
DOKSANI Y, WU J Y, DE LANGE T, et al.Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation[J].Cell,2013, 155 (2): 345-356.
SAREK G, KOTSANTIS P, RUIS P, et al.CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle[J].Nature,2019, 575 (7783): 523-527.
MACIEJOWSKI J, DE LANGE T.Telomeres in cancer: tumour suppression and genome instability[J].Nature Reviews. Molecular Cell Biology,2017, 18 (3): 175-186.
SHAY J W.Role of Telomeres and Telomerase in Aging and Cancer[J].Cancer Discovery,2016, 6 (6): 584-593.
HACKETT J A, GREIDER C W.Balancing instability: dual roles for telomerase and telomere dysfunction in tumorigenesis[J].Oncogene,2002, 21 (4): 619-626.
EBATA H, LOO T M, TAKAHASHI A.Telomere Maintenance and the cGAS-STING Pathway in Cancer[J].Cells,2022, 11 (12).
BORGES G, CRIQUI M, HARRINGTON L.Tieing together loose ends: telomere instability in cancer and aging[J].Molecular Oncology,2022, 16 (18): 3380-3396.
GAO J, PICKETT H A.Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies[J].Nature Reviews. Cancer,2022, 22 (9): 515-532.
BARTHEL F P, WEI W, TANG M, et al.Systematic analysis of telomere length and somatic alterations in 31 cancer types[J].Nature Genetics,2017, 49 (3): 349-357.
MASUTOMI K, POSSEMATO R, WONG J M Y, et al.The telomerase reverse transcriptase regulates chromatin state and DNA damage responses[J].Proceedings of the National Academy of Sciences of the United States of America,2005, 102 (23): 8222-8227.
NITTA E, YAMASHITA M, HOSOKAWA K, et al.Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism[J].Blood,2011, 117 (16): 4169-4180.
KOH C M, KHATTAR E, LEOW S C, et al.Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity[J].The Journal of Clinical Investigation,2015, 125 (5): 2109-2122.
GRONROOS E, LóPEZ-GARCíA C.Tolerance of Chromosomal Instability in Cancer: Mechanisms and Therapeutic Opportunities[J].Cancer Research,2018, 78 (23): 6529-6535.
MALKI A, ELRUZ R A, GUPTA I, et al.Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements[J].International Journal of Molecular Sciences,2020, 22 (1).
DE' ANGELIS G L, BOTTARELLI L, AZZONI C, et al.Microsatellite instability in colorectal cancer[J].Acta Bio-medica : Atenei Parmensis,2018, 89 (9-S).
PARK W-J, BAE S U, HEO Y-R, et al.Telomere shortening in non-tumorous and tumor mucosa is independently related to colorectal carcinogenesis in precancerous lesions[J].International Journal of Molecular Epidemiology and Genetics,2017, 8 (5): 53-58.
RAMPAZZO E, BERTORELLE R, SERRA L, et al.Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers[J].British Journal of Cancer,2010, 102 (8): 1300-1305.
O'HAGAN R C, CHANG S, MASER R S, et al.Telomere dysfunction provokes regional amplification and deletion in cancer genomes[J].Cancer Cell,2002, 2 (2): 149-155.
RUDOLPH K L, MILLARD M, BOSENBERG M W, et al.Telomere dysfunction and evolution of intestinal carcinoma in mice and humans[J].Nature Genetics,2001, 28 (2): 155-159.
LOPEZ-DORIGA A, VALLE L, ALONSO M H, et al.Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response[J].Biochimica Et Biophysica Acta. Molecular Basis of Disease,2018, 1864 (9 Pt B): 2992-3000.
HEAPHY C M, GAONKAR G, PESKOE S B, et al.Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial[J].The Prostate,2015, 75 (11): 1160-1166.
VALLS C, PIñOL C, REñé J M, et al.Telomere length is a prognostic factor for overall survival in colorectal cancer[J].Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland,2011, 13 (11): 1265-1272.
HERRMANN M, PUSCEDDU I, MäRZ W, et al.Telomere biology and age-related diseases[J].Clinical Chemistry and Laboratory Medicine,2018, 56 (8): 1210-1222.
GERTLER R, ROSENBERG R, STRICKER D, et al.Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma[J].Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology,2004, 22 (10): 1807-1814.
PINO M S, CHUNG D C.The chromosomal instability pathway in colon cancer[J].Gastroenterology,2010, 138 (6): 2059- 2072.
HIRANO T, HIRAYAMA D, WAGATSUMA K, et al.Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis[J].International Journal of Molecular Sciences,2020, 21 (9).
WIJNANDS A M, DE JONG M E, LUTGENS M W M D, et al.Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis[J].Gastroenterology,2021, 160 (5): 1584-1598.
CHOI C-H R, RUTTER M D, ASKARI A, et al.Forty-Year Analysis of Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis: An Updated Overview[J].The American Journal of Gastroenterology,2015, 110 (7): 1022-1034.
CANAVAN C, ABRAMS K R, MAYBERRY J.Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease[J].Alimentary Pharmacology & Therapeutics,2006, 23 (8): 1097-1104.
OLéN O, ERICHSEN R, SACHS M C, et al.Colorectal cancer in Crohn's disease: a Scandinavian population-based cohort study[J].The Lancet. Gastroenterology & Hepatology,2020, 5 (5): 475-484.
CHAKRAVARTI D, HU B, MAO X, et al.Telomere dysfunction activates YAP1 to drive tissue inflammation[J].Nature Communications,2020, 11 (1): 4766.
MOKRY L E, ZHOU S, GUO C, et al.Interleukin-18 as a drug repositioning opportunity for inflammatory bowel disease: A Mendelian randomization study[J].Scientific Reports,2019, 9 (1): 9386.
WILLIAMS M A, O'CALLAGHAN A, CORR S C.IL-33 and IL-18 in Inflammatory Bowel Disease Etiology and Microbial Interactions[J].Frontiers In Immunology,2019, 10: 1091.
WATANABE S, HIBIYA S, KATSUKURA N, et al.Importance of Telomere Shortening in the Pathogenesis of Ulcerative Colitis: A New Treatment From the Aspect of Telomeres in Intestinal Epithelial Cells[J].Journal of Crohn's & Colitis,2022, 16 (1): 109-121.
JONASSAINT N L, GUO N, CALIFANO J A, et al.The gastrointestinal manifestations of telomere-mediated disease[J].Aging Cell,2013, 12 (2): 319-323.
O'SULLIVAN J N, BRONNER M P, BRENTNALL T A, et al.Chromosomal instability in ulcerative colitis is related to telomere shortening[J].Nature Genetics,2002, 32 (2): 280-284.
AVIELLO G, KNAUS U G.ROS in gastrointestinal inflammation: Rescue Or Sabotage?[J].British Journal of Pharmacology,2017, 174 (12): 1704-1718.
BARNES R P, FOUQUEREL E, OPRESKO P L.The impact of oxidative DNA damage and stress on telomere homeostasis[J].Mechanisms of Ageing and Development,2019, 177: 37-45.
GRAHAM M K, MEEKER A.Telomeres and telomerase in prostate cancer development and therapy[J].Nature Reviews. Urology,2017, 14 (10): 607-619.
GHOSH A, SAGINC G, LEOW S C, et al.Telomerase directly regulates NF-κB-dependent transcription[J].Nature Cell Biology,2012, 14 (12): 1270-1281.
JURK D, WILSON C, PASSOS J F, et al.Chronic inflammation induces telomere dysfunction and accelerates ageing in mice[J].Nature Communications,2014, 2: 4172.
SVENSON U, GRöNLUND E, SöDERSTRöM I, et al.Telomere length in relation to immunological parameters in patients with renal cell carcinoma[J].PloS One,2013, 8 (2): e55543.
LILLEBY W, GAUDERNACK G, BRUNSVIG P F, et al.Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer[J].Cancer Immunology, Immunotherapy : CII,2017, 66 (7): 891-901.
ZANETTI M.A second chance for telomerase reverse transcriptase in anticancer immunotherapy[J].Nature Reviews. Clinical Oncology,2017, 14 (2): 115-128.
DUPERRET E K, WISE M C, TRAUTZ A, et al.Synergy of Immune Checkpoint Blockade with a Novel Synthetic Consensus DNA Vaccine Targeting TERT[J].Molecular Therapy : the Journal of the American Society of Gene Therapy,2018, 26 (2): 435-445.
ASAI A, OSHIMA Y, YAMAMOTO Y, et al.A novel telomerase template antagonist (GRN163) as a potential anticancer agent[J].Cancer Research,2003, 63 (14): 3931-3939.
BAERLOCHER G M, OPPLIGER LEIBUNDGUT E, OTTMANN O G, et al.Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia[J].The New England Journal of Medicine,2015, 373 (10): 920-928.
CHIAPPORI A A, KOLEVSKA T, SPIGEL D R, et al.A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer[J].Annals of Oncology : Official Journal of the European Society For Medical Oncology,2015, 26 (2): 354-362.
EL-DALY H, KULL M, ZIMMERMANN S, et al.Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532[J].Blood,2005, 105 (4): 1742-1749.
PILSWORTH J A, COCHRANE D R, XIA Z, et al.TERT promoter mutation in adult granulosa cell tumor of the ovary[J].Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc,2018, 31 (7): 1107-1115.
MANCINI A, XAVIER-MAGALHãES A, WOODS W S, et al.Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner[J].Cancer Cell,2018, 34 (3).