A partir de 174 échantillons tumoraux prélevés (dans le cadre du projet "The Cancer Genome Atlas") sur 174 patientes atteintes d'un cancer de l'ovaire, cette étude dresse le catalogue des anomalies génomiques et protéomiques identifiées dans les carcinomes séreux de haut grade (169 cas)

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

Zhang, Hui ; Liu, Tao ; Zhang, Zhen ; Payne, Samuel H ; Zhang, Bai ; McDermott, Jason E ; Zhou, Jian-Ying ; Petyuk, Vladislav A ; Chen, Li ; Ray, Debjit ; Sun, Shisheng ; Yang, Feng ; Chen, Lijun ; Wang, Jing ; Shah, Punit ; Cha, Seong Won ; Aiyetan, Paul ; Woo, Sunghee ; Tian, Yuan ; Gritsenko, Marina A ; Clauss, Therese R ; Choi, Caitlin ; Monroe, Matthew E ; Thomas, Stefani ; Nie, Song ; Wu, Chaochao ; Moore, Ronald J ; Yu, Kun-Hsing ; Tabb, David L ; Fenyö, David ; Bafna, Vineet ; Wang, Yue ; Rodriguez, Henry ; Boja, Emily S ; Hiltke, Tara ; Rivers, Robert C ; Sokoll, Lori ; Zhu, Heng ; Shih, Ie-Ming ; Cope, Leslie ; Pandey, Akhilesh ; Zhang, Bing ; Snyder, Michael P ; Levine, Douglas A ; Smith, Richard D ; Chan, Daniel W ; Rodland, Karin D ; Carr, Steven A ; Gillette, Michael A ; Klauser, Karl R ; Kuhn, Eric ; Mani, D. R. ; Mertins, Philipp ; Ketchum, Karen A ; Thangudu, Ratna ; Cai, Shuang ; Oberti, Mauricio ; Paulovich, Amanda G ; Whiteaker, Jeffrey R ; Edwards, Nathan J ; McGarvey, Peter B ; Madhavan, Subha ; Wang, Pei ; Whiteley, Gordon A ; Skates, Steven J ; White, Forest M ; Kinsinger, Christopher R ; Mesri, Mehdi ; Shaw, Kenna M ; Stein, Stephen E ; Rudnick, Paul ; Snyder, Michael ; Zhao, Yingming ; Chen, Xian ; Ransohoff, David F ; Hoofnagle, Andrew N ; Liebler, Daniel C ; Sanders, Melinda E ; Shi, Zhiao ; Slebos, Robbert J C. ; Zimmerman, Lisa J ; Davies, Sherri R ; Ding, Li ; Ellis, Matthew J C. ; Townsend, R.  Reid

To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the [...]

Menée à partir de 3 108 échantillons tumoraux prélevés sur des modèles murins génétiquement modifiés pour simuler un cancer chez l'humain (45 types), cette étude dresse le catalogue des anomalies chromosomiques et les compare avec des données recueillies sur des tumeurs humaines

The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis

Ben-David, Uri ; Ha, Gavin ; Khadka, Prasidda ; Jin, Xin ; Wong, Bang ; Franke, Lude ; Golub, Todd R.

Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalogue of chromosomal aberrations in cancer GEMMs. Mining this resource, we find that most chromosomal aberrations accumulate late during breast [...]

Cet article passe en revue des travaux récents suggérant que l'apoptose peut exercer une fonction oncogénique

A fate worse than death: apoptosis as an oncogenic process

Ichim, Gabriel ; Tait, Stephen W. G.

Apoptotic cell death is widely considered a positive process that both prevents and treats cancer. Although undoubtedly having a beneficial role, paradoxically, apoptosis can also cause unwanted effects that may even promote cancer. In this Opinion article we highlight some of the ways by which apoptosis can exert oncogenic functions. We argue that fully understanding this dark side will be required to optimally engage apoptosis, thereby maximizing tumour cell kill while minimizing unwanted [...]

Menée in vitro et in vivo sur des modèles de leucémie myéloïde aiguë avec réarrangements MLL, cette étude met en évidence des mécanismes par lesquels les protéines Id2 et E favorisent le développement de la maladie

Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia

Ghisi, Margherita ; Kats, Lev ; Masson, Frederick ; Li, Jason ; Kratina, Tobias ; Vidacs, Eva ; Gilan, Omer ; Doyle, Maria A ; Newbold, Andrea ; Bolden, Jessica E ; Fairfax, Kirsten A ; de Graaf, Carolyn A ; Firth, Matthew ; Zuber, Johannes ; Dickins, Ross A ; Corcoran, Lynn M ; Dawson, Mark A ; Belz, Gabrielle T ; Johnstone, Ricky W

E proteins and their antagonists, the Id proteins, are transcriptional regulators important for normal hematopoiesis. We found that Id2 acts as a key regulator of leukemia stem cell (LSC) potential in MLL-rearranged acute myeloid leukemia (AML). Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth. Importantly, MLL-AF9 itself controls the E-protein pathway by suppressing Id2 while directly activating E2-2 [...]

Menée à l'aide de modèles murins, cette étude met en évidence la dynamique clonale des cellules souches au cours de la formation d'un carcinome basocellulaire

Defining the clonal dynamics leading to mouse skin tumour initiation

Sánchez-Danés, Adriana ; Hannezo, Edouard ; Larsimont, Jean-Christophe ; Liagre, Mélanie ; Youssef, Khalil Kass ; Simons, Benjamin D. ; Blanpain, Cedric

The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, were competent to initiate tumour formation upon oncogenic hedgehog signalling. Interestingly, this [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en stimulant une autophagie, un long ARN non codant (MALAT1) favorise le processus métastatique d'un adénocarcinome canalaire du pancréas

Long noncoding RNA MALAT1 promotes aggressive pancreatic cancer proliferation and metastasis via the stimulation of autophagy

Li, Le ; Chen, Hua ; Gao, Yue ; Wang, Yong-Wei ; Zhang, Guang-quan ; Pan, Shang-ha ; Ji, Liang ; Kong, Rui ; Wang, Gang ; Jia, Yue-hui ; Bai, Xue-wei ; Sun, Bei

Recently, pancreatic ductal adenocarcinoma (PDAC) has emerged as one of the most aggressive malignant tumors with the worst prognosis. Previous studies have demonstrated that long non-coding RNA MALAT1 is increased in pancreatic cancer and is identified as a diagnostic biomarker. Nonetheless, the molecular mechanism of elevated MALAT1 levels and tumor aggressiveness remains unknown. In this study, MALAT1 was found to be highly expressed in PDAC tissues, and elevated expression was associated [...]

Menée à l'aide de modèles murins de cancer du poumon à petites cellules, cette étude met en évidence des mécanismes par lesquels la surexpression du facteur de transcription NFIB favorise la progression tumorale

Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients

Semenova, Ekaterina A ; Kwon, Min-Chul ; Monkhorst, Kim ; Song, Ji-Ying ; Bhaskaran, Rajith ; Krijgsman, Oscar ; Kuilman, Thomas ; Peters, Dennis ; Buikhuisen, Wieneke A ; Smit, Egbert F ; Pritchard, Colin ; Cozijnsen, Miranda ; van der Vliet, Jan ; Zevenhoven, John ; Lambooij, Jan-Paul ; Proost, Natalie ; van Montfort, Erwin ; Velds, Arno ; Huijbers, Ivo J ; Berns, Anton

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor, and no effective treatment is available to date. Mouse models of SCLC based on the inactivation of Rb1 and Trp53 show frequent amplifications of the Nfib and Mycl genes. Here, we report that, although overexpression of either transcription factor accelerates tumor growth, NFIB specifically promotes metastatic spread. High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively [...]

Menée in vitro et in vivo sur des modèles de cancer du sein, cette étude met en évidence des mécanismes par lesquels la tétraspanine TM4SF1 favorise la réactivation du processus métastatique dans le poumon, les os et le cerveau

Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling

Gao, Hua ; Chakraborty, Goutam ; Zhang, Zhanguo ; Akalay, Intissar ; Gadiya, Mayur ; Gao, Yaquan ; Sinha, Surajit ; Hu, Jian ; Jiang, Cizhong ; Akram, Muzaffar ; Brogi, Edi ; Leitinger, Birgit ; Giancotti, Filippo G

Genetic screening identifies the atypical tetraspanin TM4SF1 as a strong mediator of metastatic reactivation of breast cancer. Intriguingly, TM4SF1 couples the collagen receptor tyrosine kinase DDR1 to the cortical adaptor syntenin 2 and, hence, to PKCα. The latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3. This non-canonical mechanism of signaling induces the expression of SOX2 and NANOG; sustains the manifestation of cancer stem cell traits; and drives [...]