Menée à l'aide de lignées cellulaires, de modèles murins et d'échantillons tumoraux issus de patients atteints d'un cancer primitif du foie, cette étude met en évidence un mécanisme par lequel des modifications de certaines régions de microARNs tumoraux par la 8-oxoguanine favorisent ou suppriment la carcinogenèse liée aux réactions d'oxydoréduction

Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development

Eom, Sangkyeong ; Peak, Jongjin ; Park, Jongyeun ; Ahn, Seung Hyun ; Cho, You Kyung ; Jeong, Yeahji ; Lee, Hye-Sook ; Lee, Jung ; Ignatova, Elizaveta ; Lee, Sung Eun ; Hong, Yunji ; Gu, Dowoon ; Kim, Geun-Woo D. ; Lee, Dong Chan ; Hahm, Ja Young ; Jeong, Jaemin ; Choi, Dongho ; Jang, Eun-Sook ; Chi, Sung Wook

Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o8G) can change RNA–RNA interactions via o8G•A base pairing, but its regulatory roles remain elusive. Here, on the basis of o8G-induced guanine-to-thymine (o8G > T) variations featured in sequencing, we discovered widespread position-specific o8Gs in tumour microRNAs, preferentially oxidized towards 5′ end seed regions (positions 2–8) with clustered sequence patterns and [...]

Cet article résume les découvertes récentes concernant les mécanismes par lesquels des mutations de la fumarate hydratase favorisent le développement de cancers

Fumarate hydratase (FH) and cancer: a paradigm of oncometabolism

Valcarcel-Jimenez, Lorea ; Frezza, Christian

Fumarate hydratase (FH) is an enzyme of the Tricarboxylic Acid (TCA) cycle whose mutations lead to hereditary and sporadic forms of cancer. Although more than twenty years have passed since its discovery as the leading cause of the cancer syndrome Hereditary leiomyomatosis and Renal Cell Carcinoma (HLRCC), it is still unclear how the loss of FH causes cancer in a tissue-specific manner and with such aggressive behaviour. It has been shown that FH loss, via the accumulation of FH substrate [...]

Menée in vitro, cette étude met en évidence un mécanisme par lequel le détachement des cellules cancéreuses favorise l'accumulation et la sécrétion de proline

Loss of attachment promotes proline accumulation and excretion in cancer cells

Pilley, Steven E. ; Hennequart, Marc ; Vandekeere, Anke ; Blagih, Julianna ; Legrave, Nathalie M. ; Fendt, Sarah-Maria ; Vousden, Karen H. ; Labuschagne, Christiaan F.

Previous studies have revealed a role for proline metabolism in supporting cancer development and metastasis. In this study, we show that many cancer cells respond to loss of attachment by accumulating and secreting proline. Detached cells display reduced proliferation accompanied by a general decrease in overall protein production and de novo amino acid synthesis compared to attached cells. However, proline synthesis was maintained under detached conditions. Furthermore, while overall proline [...]

Menée à l'aide de lignées de cellules cancéreuses (mélanome, carcinome du côlon, tumeur de Lewis et lymphome), de modèles murins ainsi que d'échantillons de sang, de mélanomes et de tissus adjacents issus de patients, cette étude met en évidence le rôle de la protéine CD300ld dans l'immunosuppression tumorale

CD300ld on neutrophils is required for tumour-driven immune suppression

Wang, Chaoxiong ; Zheng, Xichen ; Zhang, Jinlan ; Jiang, Xiaoyi ; Wang, Jia ; Li, Yuwei ; Li, Xiaonan ; Shen, Guanghui ; Peng, Jiayin ; Zheng, Peixuan ; Gu, Yunqing ; Chen, Jiaojiao ; Lin, Moubin ; Deng, Changwen ; Gao, Hai ; Lu, Zhigang ; Zhao, Yun ; Luo, Min

The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy1,2. Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance2–4. Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo [...]

Menée à l'aide d'organoïdes, de xénogreffes et d'échantillons tumoraux prélevés sur des patients atteints d'un cancer du poumon non à petites cellules, cette étude met en évidence un mécanisme par lequel des anti-oxydants (vitamine C, vitamine E et N-Acétylcystéine) stimulent l'angiogenèse tumorale dépendante du facteur de transcription BACH1

Antioxidants stimulate BACH1-dependent tumor angiogenesis

Wang, Ting ; Dong, Yongqiang ; Huang, Zhiqiang ; Zhang, Guoqing ; Zhao, Ying ; Yao, Haidong ; Hu, Jianjiang ; Tüksammel, Elin ; Cai, Huan ; Liang, Ning ; Xu, Xiufeng ; Yang, Xijie ; Schmidt, Sarah ; Qiao, Xi ; Schlisio, Susanne ; Strömblad, Staffan ; Qian, Hong ; Jiang, Changtao ; Treuter, Eckardt ; Bergo, Martin O.

Lung cancer progression relies on angiogenesis, which is a response to hypoxia typically coordinated by hypoxia-inducible transcription factors (HIFs); but growing evidence indicate that transcriptional programs beyond HIFs control tumor angiogenesis. Here we show that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes. BACH1 is stabilized by lowering reactive oxygen species levels; consequently, angiogenesis [...]

Menée à l'aide de lignées cellulaires humaines de cancer de la bouche et d'une xénogreffe sur un modèle murin, cette étude met en évidence le rôle du canal calcique ORAI1 dans la croissance tumorale et la douleur nociceptive

The Ca2+ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain

Son, Ga-Yeon ; Tu, Nguyen Huu ; Santi, Maria Daniela ; Loya Lopez, Santiago ; Souza Bomfim, Guilherme H. ; Vinu, Manikandan ; Zhou, Fang ; Chaloemtoem, Ariya ; Alhariri, Rama ; Idaghdour, Youssef ; Khanna, Rajesh ; Ye, Yi ; Lacruz, Rodrigo S.

Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca2+ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca2+ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer [...]

Menée à l'aide de lignées cellulaires, cette étude met en évidence un mécanisme par lequel la kinase PLK1, via la phosphorylation de la polymérase theta 6, permet la réparation des cassures double brin de l'ADN durant la mitose

Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis

Gelot, Camille ; Kovacs, Marton Tibor ; Miron, Simona ; Mylne, Emilie ; Haan, Alexis ; Boeffard-Dosierre, Liza ; Ghouil, Rania ; Popova, Tatiana ; Dingli, Florent ; Loew, Damarys ; Guirouilh-Barbat, Josée ; Del Nery, Elaine ; Zinn-Justin, Sophie ; Ceccaldi, Raphael

DNA double-strand breaks (DSBs) are deleterious lesions that challenge genome integrity. To mitigate this threat, human cells rely on the activity of multiple DNA repair machineries that are tightly regulated throughout the cell cycle1. In interphase, DSBs are mainly repaired by non-homologous end joining and homologous recombination2. However, these pathways are completely inhibited in mitosis3–5, leaving the fate of mitotic DSBs unknown. Here we show that DNA polymerase theta6 (Polθ) repairs [...]

Cet article passe en revue les connaissances concernant le métabolisme du glucose dans les macrophages associés aux tumeurs (MAT), présente les profils métaboliques de différents sous-types de MAT et décrit les stratégies anticancéreuses actuelles ciblant la glycolyse des MAT

Glycolysis regulation in tumor-associated macrophages: Its role in tumor development and cancer treatment

Jiang, Guangyi ; Hong, Junjie ; Sun, Lu ; Wei, Haibin ; Gong, Wangang ; Wang, Shu ; Zhu, Jianqing

Tumor-associated macrophages constitute the main cell population in the tumor microenvironment and play a crucial role in regulating the microenvironment composition. Emerging evidence has revealed that the metabolic profile determines the tumor-associated macrophage phenotype. Tumor-associated macrophage function is highly dependent on glucose metabolism, with glycolysis being the major metabolic pathway. Recent reports have demonstrated diversity in glucose flux of tumor-associated [...]