{"id":"https://openalex.org/G2182024922","display_name":"Regulation of the human hTERT telomerase gene in normal and cancer stem cells","description":"The aim of this study is to bring together the key strategic areas of stem cell biology and cellular immortality to provide a unique environment, in which the suggested stem cell origin of cancer and the nature of the cancer stem cells will be investigated. Normal and cancer stem cells share the same main characteristic; they have the capacity for prolonged or unlimited self-renewal. This essential characteristic is due mainly to the activation of telomerase in these two cellular types. The focus of our investigation, therefore, will be to understand how telomerase is regulated in these cells which are essential for the survival of an organism, but unfortunately, also for the survival and the propagation of the malignant tumors. <br>     \u00b7 The first question we will try to answer is to determine if the hTERT gene regulation is identical in normal cells (germ and stem cells) and in tumors. The data obtained might explain why telomere length progressively decreases in stem cells, whereas it stays constant in germ cells.<br>     \u00b7 Another important question that we will address in this project is to determine whether cancer is a disease originating purely in stem cells, or whether it is generated by non-stem cells acquiring de novo self-renewal capacities. For most cancer cells telomerase is required for continuous tumor cell proliferation and malignant progression, but it is not yet clear whether telomerase is active as a consequence of selection of preexisting telomerase-positive cells during carcinogenesis or through induction of hTERT expression in cells that lack telomerase activity. The colorectal carcinogenesis was chosen as a model for this study.<br>     \u00b7Recently, a new type of stem cell has been isolated andcharacterized from a number of solid and non-solid tumors. The existence of a small population of cancer stem cells that maintain the bulk of the tumor and that are putatively responsible for the transplantability and metastatic properties of tumors might explain the failure of many anti-cancer strategies. However, there is an apparent paradox between the concepts of cancer stem cells and telomerase. In human cancers, a majority of neoplastic cells express telomerase activity and thus, they should have infinite self-renewal ability, which is apparently not the case. We postulate that, after multiple cell divisions, a down-regulation of telomerase activity occurs in almost all the tumor cells. The mechanism of hTERT regulation is remarkably complex and several conditions are necessary for its activation. Therefore, a change of only one of the parameters necessary for this activation could lead to the hTERT gene transcription arrest. We believe that an epigenetic reprogramming of CTCF binding regions could be the origin of hTERT transcription down-regulation and, as a consequence, of the tumor cell death.<br> This study would extend our knowledge regarding the molecular basis of cancer progression and could lead to the development of new approaches in cancer therapy.<br>","funder_award_id":"113505","funder":{"id":"https://openalex.org/F4320320924","display_name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi":"10.13039/501100001711"},"funded_outputs":["https://openalex.org/W859078965","https://openalex.org/W1967582727","https://openalex.org/W2109272121","https://openalex.org/W2142922561","https://openalex.org/W2145258505","https://openalex.org/W2520957811","https://openalex.org/W4392399833","https://openalex.org/W7143305175"],"funded_outputs_count":8,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":335000.0,"currency":"CHF","amount_usd":267054.97,"amount_usd_basis":"daily_rate","recipients":[{"id":"https://openalex.org/I97565354","display_name":"University of Lausanne","ror":"https://ror.org/019whta54","country_code":"CH","roles":["lead"],"share":null,"basis":"affiliation_matcher","asserted_by":"funder"}],"recipient_countries":[{"country_code":"CH","share":1.0,"amount_usd":267054.97,"basis":"organisation_location"}],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"Project funding","start_date":"2006-10-01","end_date":"2010-12-31","start_year":2006,"end_year":2010,"landing_page_url":"https://data.snf.ch/grants/grant/113505","doi":null,"provenance":"snsf","lead_investigator":{"given_name":"Benhattar,","family_name":"Jean","orcid":null,"role_start":null,"affiliation":{"name":"University of Lausanne \u2013 LA","country":"Switzerland","ids":null}},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G2182024922","primary_topic":{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.984,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.984,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"institution_awarded":[{"id":"https://openalex.org/I97565354","display_name":"University of Lausanne","ror":"https://ror.org/019whta54","country_code":"CH","type":"education","lineage":["https://openalex.org/I97565354"]}],"updated_date":"2026-10-17T03:01:12.000Z","created_date":"2026-07-13T04:27:35.000Z"}