Menée à l'aide de deux lignées cellulaires de cancer du sein hormonodépendant, cette étude met en évidence un mécanisme par lequel l'oncoprotéine SET augmente les processus transcriptionnels induits par les estrogènes en agissant sur la structure de la chromatine

The SET oncoprotein promotes estrogen-induced transcription by facilitating establishment of active chromatin

Guo, Changying ; Meza-Sosa, Karla F. ; Valle-Garcia, David ; Zhao, Guomeng ; Gao, Kun ; Yu, Liting ; Zhang, Hongying ; Chen, Yeqing ; Sun, Liang ; Rockowitz, Shira ; Wang, Shouyu ; Jiang, Sheng ; Lieberman, Judy

SET is a multifunctional histone-binding oncoprotein that regulates transcription by an unclear mechanism. Here we show that SET enhances estrogen-dependent transcription. SET knockdown abrogates transcription of estrogen-responsive genes and their enhancer RNAs. In response to 17β-estradiol (E2), SET binds to the estrogen receptor α (ERα) and is recruited to ERα-bound enhancers and promoters at estrogen response elements (EREs). SET functions as a histone H2 chaperone that dynamically [...]

Cet article analyse comment les programmes métaboliques des cellules du microenvironnement tumoral favorisent la prolifération des cellules cancéreuses, la progression de la tumeur, le processus métastatique et l'échappement immunitaire puis identifie des stratégies ciblant les voies métaboliques pour lever l'immunosuppression ou améliorer l'efficacité des immunothérapies

Metabolic programming and immune suppression in the tumor microenvironment

Arner, Emily N. ; Rathmell, Jeffrey C.

Increased glucose metabolism and uptake are characteristic of many tumors and used clinically to diagnose and monitor cancer progression. In addition to cancer cells, the tumor microenvironment (TME) encompasses a wide range of stromal, innate, and adaptive immune cells. Cooperation and competition between these cell populations supports tumor proliferation, progression, metastasis, and immune evasion. Cellular heterogeneity leads to metabolic heterogeneity because metabolic programs within the [...]

Menée à l'aide de lignées cellulaires de cancer du poumon non à petites cellules ALK+ et à l'aide de xénogreffes sur un modèle murin, cette étude met en évidence un mécanisme par lequel des variants oncogènes de fusions du gène ALK favorisent la survie des cellules cancéreuses et inhibent la cytotoxicité induite par les cellules NK via l'expression de la serpine B4

ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression

Chuang, Tzu-Po ; Lai, Wei-Yun ; Gabre, Jonatan L. ; Lind, Dan E. ; Umapathy, Ganesh ; Bokhari, Abdulmalik A. ; Bergman, Bengt ; Kristenson, Linnea ; Thorén, Fredrik B. ; Le, Anh ; Doebele, Robert C. ; Van den Eynden, Jimmy ; Palmer, Ruth H. ; Hallberg, Bengt

Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, understanding the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing [...]

Menée à l'aide de lignées cellulaires, de modèles murins ainsi que d'échantillons sanguins et d'échantillons tissulaires prélevés sur des patients atteints d'un cancer du poumon non à petites cellules, cette étude met en évidence un mécanisme par lequel l'ATPase alpha1 dépendante du calcium et du potassium, en interagissant avec l'ouabaïne endogène (une hormone adrénergique), modifie le microenvironnement et favorise l'échappement immunitaire

Na, K-ATPase α1 cooperates with its endogenous ligand to reprogram immune microenvironment of lung carcinoma and promotes immune escape

Fang, Lei ; Chen, Yan ; Li, Xin ; Li, Zijian ; Chen, Lili ; Yang, Kaiyong ; Yin, Fangzhou ; Ji, Xiaojun ; Zhou, Jiaqian ; Zeng, Tao ; Fei, Chenghao ; Ren, Chenchen ; Wang, Yulin ; Zhang, Pei ; Mu, Liyan ; Qian, Yuxuan ; Yin, Wu

Dysregulated endocrine hormones (EHs) contribute to tumorigenesis, but how EHs affect the tumor immune microenvironment (TIM) and the immunotherapy of non–small cell lung cancer (NSCLC) is still unclear. Here, endogenous ouabain (EO), an adrenergic hormone, is elevated in patients with NSCLC and closely related to tumor pathological stage, metastasis, and survival. EO promotes the suppression of TIM in vivo by modulating the expression of immune checkpoint proteins, in which programmed cell [...]

Menée in vitro et à l'aide de modèles murins de cancer mammaire, cette étude met en évidence un mécanisme par lequel le long ARN non codant BREA2 favorise le processus métastatique en perturbant l'ubiquitination de Notch-1 induite par l'ubiquitine-protéine ligase WWP2

lncRNA BREA2 promotes metastasis by disrupting the WWP2-mediated ubiquitination of Notch1

Zhang, Zhen ; Lu, Yun-Xin ; Liu, Fangzhou ; Sang, Lingjie ; Shi, Chengyu ; Xie, Shaofang ; Bian, Weixiang ; Yang, Jie-cheng ; Yang, Zuozhen ; Qu, Lei ; Chen, Shi-yi ; Li, Jun ; Yang, Lu ; Yan, Qingfeng ; Wang, Wenqi ; Fu, Peifen ; Shao, Jianzhong ; Li, Xu ; Lin, Aifu

Notch has been implicated in human cancers and is a putative therapeutic target. However, the regulation of Notch activation in the nucleus remains largely uncharacterized. Therefore, characterizing the detailed mechanisms governing Notch degradation will identify attractive strategies for treating Notch-activated cancers. Here, we report that the long noncoding RNA (lncRNA) BREA2 drives breast cancer metastasis by stabilizing the Notch1 intracellular domain (NICD1). Moreover, we reveal WW [...]

Menée à partir de l'analyse du profil transcriptionnel de cellules initiatrices de métastases cérébrales, cette étude met en évidence le rôle de l'axe HLA-G/SPAG9/STAT3 dans le processus métastatique

An HLA-G/SPAG9/STAT3 axis promotes brain metastases

Bassey-Archibong, Blessing Iquo ; Rajendra Chokshi, Chirayu ; Aghaei, Nikoo ; Kieliszek, Agata Monika ; Tatari, Nazanin ; McKenna, Dillon ; Singh, Mohini ; Kalpana Subapanditha, Minomi ; Parmar, Arun ; Mobilio, Daniel ; Savage, Neil ; Lam, Fred ; Tokar, Tomas ; Provias, John ; Lu, Yu ; Chafe, Shawn Christopher ; Swanton, Charles ; Hynds, Robert Edward ; Venugopal, Chitra ; Singh, Sheila Kumari

Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing the need for a better understanding of the disease. Herein, we analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the brain metastatic cascade—the “premetastatic” or early stage when they first colonize the brain and the established macrometastatic stage. RNA sequencing was used [...]

Cet article analyse le rôle des exosomes dans la régulation de la flore, de l'hypoxie, du processus inflammatoire et du microenvironnement immunitaire des cancers colorectaux puis examine leur intérêt thérapeutique

Exosomes: Mediators in Microenvironment of Colorectal Cancer

Yao, Jiali ; Chen, Yingrui ; Lin, Zhijie

Tumor microenvironment, the soil where tumor thrives, plays a critical role in the development and progression of colorectal cancer (CRC). Various cell signaling molecules in the environment promote tumor angiogenesis, immune tolerance and facilitate immune escape. Exosomes, as messengers between tumor and host cells, are considered key mediators involved in the tumor-accelerating environment. However, the exosome-mediated communication networks in the CRC microenvironment are still largely [...]

Cet article analyse les avantages et les inconvénients des différents modes de culture cellulaire (cultures bidimensionnelles, sphéroïdes et tumoroïdes), identifie les applications possibles des tumoroïdes pour les cancers de la tête et du cou et examine les protocoles permettant de développer ces tumoroïdes

Head and neck cancer patient-derived tumouroid cultures: opportunities and challenges

Basnayake, B. W. M. Thilini J. ; Leo, Paul ; Rao, Sudha ; Vasani, Sarju ; Kenny, Lizbeth ; Haass, Nikolas K. ; Punyadeera, Chamindie

Head and neck cancers (HNC) are the seventh most prevalent cancer type globally. Despite their common categorisation, HNCs are a heterogeneous group of malignancies arising in various anatomical sites within the head and neck region. These cancers exhibit different clinical and biological manifestations, and this heterogeneity also contributes to the high rates of treatment failure and mortality. To evaluate patients who will respond to a particular treatment, there is a need to develop in [...]

Cet article passe en revue les différents modèles précliniques pour les carcinomes épidermoïdes de la tête et du cou

Preclinical models in head and neck squamous cell carcinoma

Chaves, Patricia ; Garrido, Maria ; Oliver, Javier ; Perez-Ruiz, Elisabeth ; Barragan, Isabel ; Rueda-Domínguez, Antonio

Head and neck cancer is the sixth most frequent cancer type. Drug resistance and toxicity are common challenges of the existing therapies, making the development of reliable preclinical models essential for the study of the involved molecular mechanisms as well as for eventual intervention approaches that improve the clinical outcome. Preclinical models of head and neck squamous cell carcinoma have been traditionally based on cell lines and murine models. In this review, we will go over the [...]