Menée à l'aide de lignées cellulaires d'adénocarcinome pulmonaire, de xénogreffes sur des modèles murins et de données de séquençage d'échantillons tumoraux ou d'échantillons tissulaires sains, cette étude met en évidence le rôle de suppresseur de tumeur de l'hélicase SHPRH ainsi qu'une association entre le niveau d'expression de cette dernière et la tolérance des cellules cancéreuses aux dommages causés à l'ADN

Integrative genomics identifies SHPRH as a tumor suppressor gene in lung adenocarcinoma that regulates DNA damage response

Nagelberg, Amy L. ; Sihota, Tianna S. ; Chuang, Yu-Chi ; Shi, Rocky ; Chow, Justine L. M. ; English, John ; MacAulay, Calum ; Lam, Stephen ; Lam, Wan L. ; Lockwood, William W.

Background : Identification of driver mutations and development of targeted therapies has considerably improved outcomes for lung cancer patients. However, significant limitations remain with the lack of identified drivers in a large subset of patients. Here, we aimed to assess the genomic landscape of lung adenocarcinomas (LUADs) from individuals without a history of tobacco use to reveal new genetic drivers of lung cancer. Methods : Integrative genomic analyses combining whole-exome [...]

Menée à l'aide de lignées cellulaires, d'organoïdes, de xénogreffes sur des modèles murins et d'échantillons tumoraux issus de patients atteints d'un cancer colorectal, cette étude met en évidence un mécanisme par lequel l'ion ferrique Fe3+, en réactivant la télomérase, favorise la carcinogenèse colorectale

Iron-(Fe3+) dependent reactivation of telomerase drives colorectal cancers

Shanmugam, Raghuvaran ; Majee, Prativa ; Shi, Wei ; Ozturk, Mert Burak ; Vaiyapuri, Thamil Selvan. ; Idzham, Khaireen ; Raju, Anandhkumar ; Shin, Seung Hee ; Fidan, Kerem ; Low, Joo-Leng ; Chua, Joelle Yi Heng. ; Kong, Yap Choon. ; Qi, Ong Yue. ; Tan, Emile ; Chok, Aik Yong ; Seow-En, Isaac ; Wee, Ian ; Macalinao, Dominique Camat. ; Chong, Dawn Qingqing. ; Chang, Hong Yun ; Lee, Fiona ; Leow, Wei Qiang ; Murata-Hori, Maki ; Xiaoqian, Zhang ; Shumei, Chia ; Tan, Chris Soon Heng. ; DasGupta, Ramanuj ; Tan, Iain Beehuat ; Tergaonkar, Vinay

Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with increased risk of colorectal carcinogenesis, yet the mechanistic basis of how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh colorectal cancer (CRC) samples we identify Pirin, an iron sensor, that overcomes a rate-limiting step in oncogenesis, by re-activating the dormant human-reverse-transcriptase (hTERT) subunit of telomerase holoenzyme in an [...]

Menée à l'aide de lignées cellulaires et de tissus de carcinomes épidermoïdes issus de patients atteints d'une leucémie lymphoïde chronique, cette étude met en évidence un mécanisme par lequel les cellules leucémiques, via l'activation du récepteur à tyrosine kinase AXL, favorisent la progression du carcinome épidermoïde

Aberrant activation of AXL may drive progression of squamous cell carcinoma in CLL patients: a mechanistic study with clinical implications

Sinha, Sutapa ; Guo, Ray ; Del Busso, Miles D. ; Han, Weiguo ; Boysen, Justin ; Wellik, Linda E. ; Ghosh, Asish K. ; Kay, Neil E.

Background : Occurrence of squamous cell carcinoma (SCC) even in early-stage, untreated chronic lymphocytic leukemia (CLL) patients can be a significant morbidity issue with occasional transformation into metastatic skin lesions. Methods : CLL cells and extracellular vesicles (EVs) from CLL patients’ blood/plasma were purified and used. Expression/activation of AXL and its functions in normal keratinocytes (HEKa) were assessed in vitro co-culture system and in SCC tissues. Results : We detected [...]

Menée à l'aide de lignées cellulaires de cancer du poumon et d'une xénogreffe sur un modèle murin, cette étude met en évidence un mécanisme par lequel la sirtuine 7, une désacétylase NAD-dépendante, favorise la progression tumorale en déstabilisant le suppresseur de tumeur ARF

SIRT7 promotes lung cancer progression by destabilizing the tumor suppressor ARF

Kumari, Poonam ; Tarighi, Shahriar ; Fuchshuber, Eva ; Li, Luhan ; Fernández-Duran, Irene ; Wang, Meilin ; Ayoson, Joshua ; Castelló-García, Jose Manuel ; Gámez-García, Andrés ; Espinosa-Alcantud, Maria ; Sreenivasan, Krishnamoorthy ; Guenther, Stefan ; Olivella, Mireia ; Savai, Rajkumar ; Yue, Shijing ; Vaquero, Alejandro ; Braun, Thomas ; Ianni, Alessandro

Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts [...]

Cet article passe en revue les avancées récentes concernant le rôle du microbiote de l'estomac dans le développement des cancers gastriques puis examine l'intérêt de ce microbiote pour diagnostiquer la maladie, établir un pronostic et améliorer l'efficacité des traitements

Stomach microbiota in gastric cancer development and clinical implications

Zeng, Ruijie ; Gou, Hongyan ; Lau, Harry Cheuk Hay ; Yu, Jun

Gastric cancer (GC) is one of the most common malignancies and a prominent cause of cancer mortality worldwide. A distinctive characteristic of GC is its intimate association with commensal microbial community. Although Helicobacter pylori is widely recognised as an inciting factor of the onset of gastric carcinogenesis, increasing evidence has indicated the substantial involvement of microbes that reside in the gastric mucosa during disease progression. In particular, dysregulation in gastric [...]

Cet article passe en revue les mécanismes de la promotion tumorale et identifie des cibles moléculaires potentielles permettant d'enrayer le développement de certains cancers

Tumor Promoters and Opportunities for Molecular Cancer Prevention

Hill, William ; Weeden, Clare E. ; Swanton, Charles

Environmental carcinogens increase cancer incidence via both mutagenic and non-mutagenic mechanisms. There are over 500 known or suspected carcinogens classified by the International Agency for Research on Cancer. Sequencing of both cancerous and histologically non-cancerous tissue has been instrumental in improving our understanding of how environmental carcinogens cause cancer. Understanding how and defining which environmental or lifestyle exposures drive cancer will support cancer [...]

Cet article décrit les projets de recherche, le centre de coordination et les objectifs de MeDOC, un programme de recherche concernant les mécanismes pouvant expliquer la relation entre obésité, dérégulation métabolique et cancers

Metabolic dysregulation and cancer risk program (MeDOC): a transdisciplinary approach to Obesity-Associated cancers

Kim Lam, Tram ; Daschner, Phil ; Ishibe, Naoko ; Wali, Anil ; Hall, Kara ; Czajkowski, Susan ; Mahabir, Somdat ; Watson, Joanna M ; Nebeling, Linda ; Ross, Sharon ; Sauter, Edward

With the escalating prevalence of obesity, the association between obesity and cancer is a growing public health concern. Obesity will soon surpass tobacco smoking as the most important preventable cause of cancer. Obesity-driven mechanisms can alter cell functions to induce metabolic changes, chronic inflammation, and insulin resistance that are believed to contribute to cancer risk and development; yet the specific underlying biological mechanisms of obesity-related cancer development are [...]

Cet article passe en revue les mécanismes par lesquels le microbiome pulmonaire influence la carcinogenèse, analyse le rôle de ses interactions avec l'hôte dans la réponse immunitaire puis examine son intérêt dans le diagnostic d'un cancer du poumon

Lung Microbiome in Lung Cancer: A New Horizon in Cancer Study

Kashyap, Pragya ; Dutt, Naveen ; Ahirwar, Dinesh K. ; Yadav, Pankaj

Lung cancer is the second most prevalent cancer worldwide and a leading cause of cancer-related deaths. Recent technological advancements have revealed that the lung microbiome, previously thought to be sterile, is host to various microorganisms. The association between the lung microbiome and lung cancer initiation, progression, and metastasis is complex and contradictory. However, disruption in the homeostasis of microbiome compositions correlated with the increased risk of lung cancer. This [...]

Cet article passe en revue les études sur les mutations génétiques constitutionnelles associées aux cancers du poumon, examine les implications biologiques et thérapeutiques de ces mutations puis analyse l'intérêt clinique des tests PRS

Biological and therapeutic implications of the cancer-related germline mutation landscape in lung cancer

Panagiotou, Emmanouil ; Vathiotis, Ioannis A. ; Makrythanasis, Periklis ; Hirsch, Fred ; Sen, Triparna ; Syrigos, Konstantinos

Although smoking is the primary cause of lung cancer, only about 15% of lifelong smokers develop the disease. Moreover, a substantial proportion of lung cancer cases occur in never-smokers, highlighting the potential role of inherited genetic factors in the cause of lung cancer. Lung cancer is significantly more common among those with a positive family history, especially for early-onset disease. Therefore, the presence of pathogenic germline variants might act synergistically with [...]