ABSTRACT

Telomerase is a key enzyme for cell survival that prevents telomere shortening and the subsequent cellular senescence that is observed after many rounds of cell division. In contrast, inactivation of telomerase is observed in most cells of the adult liver. Absence of telomerase activity and shortening of telomeres has been implicated in hepatocyte senescence and the development of cirrhosis, a chronic liver disease that can lead to hepatocellular carcinoma (HCC) development. During hepatocarcinogenesis, telomerase reactivation is required to enable the uncontrolled cell proliferation that leads to malignant transformation and HCC development. Part of the telomerase complex, telomerase reverse transcriptase, is encoded by TERT, and several mechanisms of telomerase reactivation have been described in HCC that include somatic TERT promoter mutations, TERTamplification, TERT translocation and viral insertion into the TERTgene. An understanding of the role of telomeres and telomerase in HCC development is important to develop future targeted therapies and improve survival of this disease. In this Review, the roles of telomeres and telomerase in liver carcinogenesis are discussed, in addition to their potential translation to clinical practice as biomarkers and therapeutic targets.

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Eric Letouzé and Stefano Caruso from our lab will present their works tomorrow at the CRC Scientific Day!

Don’t miss this day with high level science from our Research Center !

More informations on CRC website:

http://www.crc.jussieu.fr/journee_scientifique_du_crc.html

The last work of Sandra Rebouissou group is newly accepted for publication in Gastroenterology.

Entitled, “Analysis of Liver Cancer Cell Lines Identifies Agents With Likely Efficacy Against Hepatocellular Carcinoma and Markers of Response” it is the first study to provide a comprehensive molecular characterization of most widely used liver cancer cell lines. All the data are available at : www.lccl.zucmanlab.com

Article available on Gastroenterology website.

Yuna Blum, from Ligue National Contre le Cancer and Didier Jean group used a deconvolution approach and show that molecular gradients shed new light on the intra-tumor heterogeneity of malignant mesothelioma.

Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both onhistology and molecular profiling. Histology addresses inter-tumor and intra-tumor hetero-geneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, acombination of the former two types. Molecular profiling studies have not addressed intra-tumor heterogeneity in MPM to date. Here, we use a deconvolution approach and show thatmolecular gradients shed new light on the intra-tumor heterogeneity of MPM, leading to areconsideration of MPM molecular classifications. We show that each tumor can bedecomposed as a combination of epithelioid-like and sarcomatoid-like components whoseproportions are highly associated with the prognosis. Moreover, we show that this moresubtle way of characterizing MPM heterogeneity provides a better understanding of theunderlying oncogenic pathways and the related epigenetic regulation and immune andstromal contexts. We discuss the implications of thesefindings for guiding therapeuticstrategies, particularly immunotherapies and targeted therapies.

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After having published the excellent booklet devoted to the portraits of “40 remarkable women scientists”, Médecine/Sciences continues to put women in the spotlight by opening a new video section on its website, “Les entretiens de m/s”, which features women scientists for their first cycle whose dynamism and passionate commitment are communicative. Jessica, our director had the opportunity to talk about liver tumors and women in sciences trough this interview!