A partir d'échantillons tumoraux prélevés sur 51 patients atteints d'un lymphome T/NK et 43 patients atteints d'un lymphome T gamma delta, cette étude identifie la présence fréquente de mutations activatrives des gènes STAT3 et STAT5B

Activating mutations of STAT5B and STAT3 in lymphomas derived from gamma-delta-T or NK cells

Kucuk, Can ; Jiang, Bei ; Hu, Xiaozhou ; Zhang, Wenyan ; Chan, John K. C. ; Xiao, Wenming ; Lack, Nathan ; Alkan, Can ; Williams, John C. ; Avery, Kendra N. ; Kavak, Pınar ; Scuto, Anna ; Sen, Emel ; Gaulard, Philippe ; Staudt, Lou ; Iqbal, Javeed ; Zhang, Weiwei ; Cornish, Adam ; Gong, Qiang ; Yang, Qunpei ; Sun, Hong ; d’Amore, Francesco ; Leppä, Sirpa ; Liu, Weiping ; Fu, Kai ; de Leval, Laurence ; McKeithan, Timothy ; Chan, Wing C.

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to [...]

A partir d'échantillons prélevés dans des métastases ganglionnaires de 29 patients atteints d'un carcinome épidermoïde cutané, cette étude identifie la présence de mutations dans plusieurs gènes et suggère l'intérêt de diverses thérapies ciblées faisant l'objet d'essais cliniques dans les carcinomes épidermoïdes métastatiques du poumon et de la tête et du cou

Genomic analysis of metastatic cutaneous squamous cell carcinoma

Li, Yvonne Y ; Hanna, Glenn J. ; Laga, Alvaro C. ; Haddad, Robert I ; Lorch, Jochen H ; Hammerman, Peter S.

Purpose: A rare 5% of cutaneous squamous cell carcinomas metastasize, lack FDA-approved therapies, and carry a poor prognosis. Our aim was to identify recurrent genomic alterations in this little-studied population of metastatic cSCCs. Experimental Design: We performed targeted sequencing of 504 cancer-associated genes on lymph node metastases in 29 patients with cSCC and identified mutations and somatic copy number alterations associated with metastatic cSCC. We determined significantly [...]

Menée in vitro, cette étude met en évidence des mécanismes par lesquels, via l'oncoprotéine LAPTM4B, le récepteur inactif EGFR régule le processus d'autophagie et favorise la survie des cellules tumorales en situation de stress métabolique

A Kinase-Independent Role for EGF Receptor in Autophagy Initiation

Tan, Xiaojun ; Thapa, Narendra ; Sun, Yue ; Anderson, Richard A

The epidermal growth factor receptor (EGFR) is upregulated in numerous human cancers. Inhibition of EGFR signaling induces autophagy in tumor cells. Here, we report an unanticipated role for the inactive EGFR in autophagy initiation. Inactive EGFR interacts with the oncoprotein LAPTM4B that is required for the endosomal accumulation of EGFR upon serum starvation. Inactive EGFR and LAPTM4B stabilize each other at endosomes and recruit the exocyst subcomplex containing Sec5. We show that inactive [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels la kinase issue de la fusion des gènes FGFR3 et BAIAP2L1 exerce une fonction oncogénique

Mechanism of oncogenic signal activation by the novel fusion kinase FGFR3-BAIAP2L1

Nakanishi, Yoshito ; Akiyama, Nukinori ; Tsukaguchi, Toshiyuki ; Fujii, Toshihiko ; Satoh, Yasuko ; Ishii, Nobuya ; Aoki, Masahiro

Recent cancer genome profiling studies have identified many novel genetic alterations, including rearrangements of genes encoding fibroblast growth factor receptor (FGFR) family members. However, most fusion genes are not functionally characterized, and their potentials in targeted therapy are unclear. We investigated a recently discovered gene fusion between FGFR3 and BAI1-associated protein 2-like 1 (BAIAP2L1). We identified 4 bladder cancer patients and 2 lung cancer patients harboring the [...]

Cet article passe en revue les travaux récents sur le rôle des protéines RUNX dans le développement d'un cancer

The RUNX family: developmental regulators in cancer

Ito, Yoshiaki ; Bae, Suk-Chul ; Chuang, Linda Shyue Huey

RUNX proteins belong to a family of metazoan transcription factors that serve as master regulators of development. They are frequently deregulated in human cancers, indicating a prominent and, at times, paradoxical role in cancer pathogenesis. The contextual cues that direct RUNX function represent a fast-growing field in cancer research and could provide insights that are applicable to early cancer detection and treatment. This Review describes how RUNX proteins communicate with key signalling [...]

Cet article passe en revue les travaux récents sur les différents modèles permettant de rendre compte du processus métastatique

Using tumour phylogenetics to identify the roots of metastasis in humans

Naxerova, Kamila ; Jain, Rakesh K.

In cancer, much uncertainty remains regarding the origins of metastatic disease. Models of metastatic progression offer competing views on when dissemination occurs (at an early or late stage of tumour development), whether metastases at different sites arise independently and directly from the primary tumour or give rise to each other, and whether dynamic cell exchange occurs between synchronously growing lesions. Although it is probable that many routes can lead to the establishment of [...]

Cet article passe en revue les travaux récents sur le rôle des protéines YAP et TAZ, liées à la voie de signalisation Hippo, dans la progression d'un cancer

The emerging roles of YAP and TAZ in cancer

Moroishi, Toshiro ; Hansen, Carsten Gram ; Guan, Kun-Liang

Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are the major downstream effectors of the Hippo pathway, which regulates tissue homeostasis, organ size, regeneration and tumorigenesis. In this Progress article, we summarize the current understanding of the biological functions of YAP and TAZ, and how the regulation of these two proteins can be disrupted in cancer. We also highlight recent findings on their expanding role in cancer progression and [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels le récepteur à activité tyrosine kinase ERBB3 contribue au développement, à la progression et à la réponse thérapeutique d'un adénocarcinome du poumon présentant un gène EGFR muté

ERBB3 Independent Activation of the PI3K Pathway in EGFR Mutant Lung Adenocarcinomas

Song, Xiaoling ; Fan, Pang-Dian ; Bantikassegn, Amlak ; Guha, Udayan ; Threadgill, David W. ; Varmus, Harold ; Politi, Katerina

ERBB3, a member of the Epidermal Growth Factor Receptor (EGFR) family of receptor tyrosine kinases, has been implicated in activation of the phosphatidyl-inositol 3-kinase (PI3K) pathway in human lung adenocarcinomas driven by EGFR mutations. We investigated the contribution of ERBB3 to the initiation, progression and therapeutic response of EGFR-induced lung adenocarcinomas using tetracycline- and tamoxifen- inducible transgenic mouse models. Deletion of Erbb3 at the time of induction of [...]

Menée à l'aide de modèles murins, cette étude met en évidence le rôle joué par deux micro-ARNs, miR-551a et miR-483, dans la régulation des métastases hépatiques d'un cancer colorectal

Extracellular Metabolic Energetics Can Promote Cancer Progression

Loo, Jia Min ; Scherl, Alexis ; Nguyen, Alexander ; Man, Fung Ying ; Weinberg, Ethan ; Zeng, Zhaoshi ; Saltz, Leonard ; Paty, Philip B ; Tavazoie, Sohail F

Colorectal cancer primarily metastasizes to the liver and globally kills over 600,000 people annually. By functionally screening 661 microRNAs (miRNAs) in parallel during liver colonization, we have identified miR-551a and miR-483 as robust endogenous suppressors of liver colonization and metastasis. These miRNAs convergently target creatine kinase, brain-type (CKB), which phosphorylates the metabolite creatine, to generate phosphocreatine. CKB is released into the extracellular space by [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels des cellules relâchées par une tumeur mammaire s'établissent dans une niche osseuse et forment des micrométastases

The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

Wang, Hai ; Yu, Cuijuan ; Gao, Xia ; Welte, Thomas ; Muscarella, Aaron M ; Tian, Lin ; Zhao, Hong ; Zhao, Zhen ; Du, Shiyu ; Tao, Jianning ; Lee, Brendan ; Westbrook, Thomas F ; Wong, Stephen T C. ; Jin, Xin ; Rosen, Jeffrey M ; Osborne, C.  Kent ; Zhang, Xiang H F.

Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes [...]

A partir de bases de données portant sur des échantillons tumoraux prélevés sur des patients atteints d'une tumeur solide (18 types différents), cette étude identifie la présence fréquente de gènes mutés en association avec une activité cytolytique induite localement par des cellules du système immunitaire

Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity

Rooney, Michael S ; Shukla, Sachet A ; Wu, Catherine J ; Getz, Gad ; Hacohen, Nir

How the genomic landscape of a tumor shapes and is shaped by anti-tumor immunity has not been systematically explored. Using large-scale genomic data sets of solid tissue tumor biopsies, we quantified the cytolytic activity of the local immune infiltrate and identified associated properties across 18 tumor types. The number of predicted MHC Class I-associated neoantigens was correlated with cytolytic activity and was lower than expected in colorectal and other tumors, suggesting immune-mediated [...]

Cette étude présente les caractéristiques d'une lignée cellulaire issue de cellules tumorales circulantes prélevées sur un patient atteint d'un cancer du côlon

Establishment and characterization of a cell line from human circulating colon cancer cells

Cayrefourcq, Laure ; Mazard, Thibault ; Joosse, Simon ; Solassol, Jérôme ; Ramos, Jeanne ; Assenat, Eric ; Schumacher, Udo ; Costes, Valerie ; Maudelonde, Thierry ; Pantel, Klaus ; Alix-Panabières, Catherine

Circulating tumor cells (CTCs) in blood are promising new biomarkers potentially useful for prognostic prediction and monitoring of therapies in patients with solid tumors including colon cancer. Moreover, CTC research opens a new avenue for understanding the biology of metastasis in cancer patients. However, an in-depth investigation of CTCs is hampered by the very low number of these cells, especially in the blood of colorectal cancer patients. Thus, the establishment of cell cultures and [...]