Menée sur des échantillons de tumeurs gastriques et de tissus non cancéreux prélevés sur des patients asiatiques, cette étude de séquençage des ARNs messagers et des micro-ARNs suggère que la protéine AMPK-α, qui intervient dans la régulation du métabolisme, pourrait servir de cible thérapeutique dans cette population

AMPKα modulation in cancer progression: multilayer integrative transcriptome analysis in Asian gastric cancer

Kim, Yon Hui S ; Liang, Han ; Liu, Xiuping ; Lee, Ju-Seog ; Cho, Jae Yong ; Cheong, Jae-Ho ; Kim, Hoguen ; Li, Min ; Downey, Thomas ; Dyer, Matthew D ; Sun, Yongming ; Sun, Jingtao ; Beasley, Ellen M ; Chung, Hyun Cheol ; Noh, Sung Hoon ; Weinstein, John N ; Liu, Chang-Gong ; Powis, Garth

Gastric cancer is the most common cancer in Asia and most developing countries. Despite the use of multimodality therapeutics, it remains the second leading cause of cancer death in the world. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens, generating 680 million informative short reads to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs [...]

Cet article passe en revue les travaux récents sur la formation de cellules cancéreuses polyploïdes en association avec le phénomène de cannibalisme cellulaire

Mechanisms of Ploidy Increase in Human Cancers: A New Role for Cell Cannibalism

Krajcovic, Matej ; Overholtzer, Michael

Aneuploidy is a hallmark of human cancers originating from abnormal mitoses. Many aneuploid cancer cells also have greater-than-diploid DNA content, suggesting that polyploidy is a common precursor to aneuploidy during tumor progression. Polyploid cells can originate from cell fusion, endoreplication, and cytokinesis failure. Recently we found that cell cannibalism by entosis, a form of cell engulfment involving live cells, also leads to polyploidy, as internalized cells disrupt cytokinesis of [...]

Menée sur 53 patients atteints d'une néoplasie myéloproliférative qui s'est transformée en leucémie, cette étude de séquençage identifie des mutations du gène SRSF2 associées à la transformation

Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms reveals recurrent SRSF2 mutations which are associated with adverse outcome

Zhang, Su-Jiang ; Rampal, Raajit ; Manshouri, Taghi ; Patel, Jay ; Mensah, Nana ; Kayserian, Andrew ; Hricik, Todd ; Heguy, Adriana ; Hedvat, Cyrus ; Gonen, Mithat ; Kantarjian, Hagop ; Levine, Ross L. ; Abdel-Wahab, Omar ; Verstovsek, Srdan

Leukemic transformation (LT) of myeloproliferative neoplasms (MPNs) is associated with a poor prognosis and resistance to therapy. Although previous candidate genetic studies have identified mutations in MPN patients who develop acute leukemia, the complement of genetic abnormalities in MPN patients who undergo LT is not known nor have specific molecular abnormalities been shown to have clinical relevance in this setting. We performed high throughput resequencing of 22 genes in 53 patients with [...]

Cet article passe en revue les travaux récents sur le métabolisme des cellules cancéreuses et suggère que les anomalies métaboliques constituent une caractéristique essentielle du cancer

Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate

Ward, Patrick S ; Thompson, Craig B

Cancer metabolism has long been equated with aerobic glycolysis, seen by early biochemists as primitive and inefficient. Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria but result from oncogene-directed metabolic reprogramming required to support anabolic growth. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation. No longer can [...]

Menée in vitro, cette étude met en évidence le rôle de suppresseur de tumeurs joué par CD45, une protéine à activité tyrosine-phosphatase codée par le gène PTPRC, dans la leucémie aiguë lymphoblastique T

Mutation of the receptor tyrosine phosphatase PTPRC (CD45) in T-cell acute lymphoblastic leukemia

Porcu, Michaël ; Kleppe, Maria ; Gianfelici, Valentina ; Geerdens, Ellen ; De Keersmaecker, Kim ; Tartaglia, Marco ; Foà, Robin ; Soulier, Jean ; Cauwelier, Barbara ; Uyttebroeck, Anne ; Macintyre, Elizabeth ; Vandenberghe, Peter ; Asnafi, Vahid ; Cools, Jan

The protein tyrosine phosphatase CD45, encoded by the PTPRC gene, is well known as a regulator of B- and T-cell receptor signaling. In addition, CD45 negatively regulates JAK family kinases downstream of cytokine receptors. Here, we report the presence of CD45 inactivating mutations in T-cell acute lymphoblastic leukemia (T-ALL). Loss-of-function mutations of CD45 were detected in combination with activating mutations in IL7R, JAK1 or LCK, and downregulation of CD45 expression caused increased [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence le rôle joué par l'expression du gène PFKFB4, un régulateur de l'activité glycolytique, dans le cancer métastatique de la prostate

Functional Metabolic Screen Identifies 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 as an Important Regulator of Prostate Cancer Cell Survival

Ros, Susana ; Santos, Claudio R. ; Moco, Sofia ; Baenke, Franziska ; Kelly, Gavin ; Howell, Michael ; Zamboni, Nicola ; Schulze, Almut

Alterations in metabolic activity contribute to the proliferation and survival of cancer cells. We investigated the effect of siRNA-mediated gene silencing of 222 metabolic enzymes, transporters, and regulators on the survival of 3 metastatic prostate cancer cell lines and a nonmalignant prostate epithelial cell line. This approach revealed significant complexity in the metabolic requirements of prostate cancer cells and identified several genes selectively required for their survival. Among [...]

Cet article passe en revue les travaux récents sur les cellules souches cancéreuses et discute de la pertinence de ce modèle dans divers types de cancer

Cancer Stem Cells: Impact, Heterogeneity, and Uncertainty

Magee, Jeffrey A ; Piskounova, Elena ; Morrison, Sean J

The differentiation of tumorigenic cancer stem cells into nontumorigenic cancer cells confers heterogeneity to some cancers beyond that explained by clonal evolution or environmental differences. In such cancers, functional differences between tumorigenic and nontumorigenic cells influence response to therapy and prognosis. However, it remains uncertain whether the model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which [...]

Cet article passe en revue le rôle du micro-environnement tumoral et de ses interactions avec les cellules cancéreuses dans la progression d'un cancer

Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

Hanahan, Douglas ; Coussens, Lisa M

Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of ostensibly normal tissue and bone marrow-derived (stromal) cells are recruited to constitute tumorigenic microenvironments. Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types. Their contributory functions to [...]

Menée in vitro sur des lignées cellulaires de cancer de la prostate, cette étude identifie un mécanisme par lequel la surexpression du gène Myb favorise la transition épithélio-mésenchymateuse et la résistance à la castration

Myb overexpression overrides androgen depletion-induced cell cycle arrest and apoptosis in prostate cancer cells, and confers aggressive malignant traits: potential role in castration resistance

Srivastava, Sanjeev K. ; Bhardwaj, Arun ; Singh, Seema ; Arora, Sumit ; McClellan, Steven ; Grizzle, William E. ; Reed, Eddie ; Singh, Ajay P.

Myb, a cellular progenitor of v-Myb oncogenes, is amplified in prostate cancer and exhibits greater amplification frequency in hormone-refractory disease. Here, we have investigated the functional significance of Myb in prostate cancer. Our studies demonstrate Myb expression in all prostate cancer cell lines (LNCaP, C4-2, PC3 and DU145) examined, whereas it is negligibly expressed in normal/benign prostate epithelial cells (RWPE1 and RWPE2). Notably, Myb is significantly upregulated, both at [...]