Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant l'activation d'une enzyme de la voie de signalisation des pentoses phosphates (G6PD), le facteur de transcription YY1 favorise la prolifération des cellules cancéreuses

Transcription factor YY1 promotes cell proliferation by directly activating the pentose phosphate pathway

Wu, Shourong ; Wang, Huimin ; Li, Yanjun ; Xie, Yudan ; Huang, Can ; Zhao, Hezhao ; Miyagishi, Makoto ; Kasim, Vivi

Tumor cells alter their metablosim to meet their demand for macromolecules, support a high rate of proliferation as well as cope with oxidative stress. The transcription factor yin yang 1 (YY1) is upregulated in various types of tumors and is crucial for tumor cell proliferation and metastasis. However, its role in tumor cell metabolic reprogramming is poorly understood. Here we show that YY1 alters tumor cell metabolism by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting [...]

Menée à l'aide de la technologie CRISPR sur des lignées cellulaires de cancer du poumon à petites cellules, cette étude met en évidence le rôle joué par une surexpression du facteur de transcription POU2F3 dans un sous-ensemble de lignées cellulaires définissant un variant de la maladie

POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer

Huang, Yu-Han ; Klingbeil, Olaf ; He, Xue-Yan ; Wu, Xiaoli S. ; Arun, Gayatri ; Lu, Bin ; Somerville, Tim D.D. ; Milazzo, Joseph P. ; Wilkinson, John E. ; Demerdash, Osama E. ; Spector, David L. ; Egeblad, Mikala ; Shi, Junwei ; Vakoc, Christopher R.

Small cell lung cancer (SCLC) is widely considered to be a tumor of pulmonary neuroendocrine cells; however, a variant form of this disease has been described that lacks neuroendocrine features. Here, we applied domain-focused CRISPR screening to human cancer cell lines to identify the transcription factor (TF) POU2F3 (POU class 2 homeobox 3; also known as SKN-1a/OCT-11) as a powerful dependency in a subset of SCLC lines. An analysis of human SCLC specimens revealed that POU2F3 is expressed [...]

Menée in vitro et in vivo sur des modèles de glioblastome, cette étude met en évidence des mécanismes par lesquels, via des vésicules extracellulaires comportant un facteur d'épissage RBM11, des cellules cancéreuses en apoptose favorisent de façon paradoxale la prolifération des cellules tumorales et la résistance thérapeutique

Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors

Pavlyukov, Marat S. ; Yu, Hai ; Bastola, Soniya ; Minata, Mutsuko ; Shender, Victoria O. ; Lee, Yeri ; Zhang, Suojun ; Wang, Jia ; Komarova, Svetlana ; Wang, Jun ; Yamaguchi, Shinobu ; Alsheikh, Heba Allah ; Shi, Junfeng ; Chen, Dongquan ; Mohyeldin, Ahmed ; Kim, Sung-Hak ; Shin, Yong Jae ; Anufrieva, Ksenia ; Evtushenko, Evgeniy G. ; Antipova, Nadezhda V. ; Arapidi, Georgij P. ; Govorun, Vadim ; Pestov, Nikolay B. ; Shakhparonov, Mikhail I. ; Lee, L. James ; Nam, Do-Hyun ; Nakano, Ichiro

Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter RNA splicing in [...]

Menée sur des lignées cellulaires de cancer colorectal et à l'aide d'un modèle animal (poisson-zèbre), cette étude met en évidence des mécanismes par lesquels, lorsqu'ils expriment l'endogline (un co-récepteur de la famille TGF-bêta), les fibroblastes associés au cancer favorisent la progression tumorale et le processus métastatique

Endoglin expression on cancer-associated fibroblasts regulates invasion and stimulates colorectal cancer metastasis

Paauwe, Madelon ; Schoonderwoerd, Mark J. A. ; Helderman, Roxan F. C. P. A. ; Harryvan, Tom J. ; Groenewoud, Arwin ; van Pelt, Gabi W. ; Bor, Rosalie ; Hemmer, Danielle M. ; Versteeg, Henri H. ; Snaar-Jagalska, Ewa ; Theuer, Charles P. ; Hardwick, James C. H. ; Sier, Cornelis F. M. ; ten Dijke, Peter ; Hawinkels, Lukas J. A. C.

Purpose: Cancer-associated fibroblasts (CAFs) are a major component of the colorectal cancer (CRC) tumor microenvironment. CAFs play an important role in tumor progression and metastasis, partly through the transforming growth factor-β (TGF-β) signaling pathway. We investigated whether the TGF-β family co-receptor endoglin is involved in CAF-mediated invasion and metastasis. Experimental design: CAF-specific endoglin expression was studied in CRC resection specimens using immunohistochemistry [...]

Menée in vitro et in vivo sur des modèles de cancer du sein, cette étude met en évidence des mécanismes par lesquels, si la protéine FBXO22 favorise la prolifération des cellules d'une tumeur primitive, elle inhibe également le processus métastatique

FBXO22 possesses both pro-tumorigenic and anti-metastatic roles in breast cancer progression

Sun, Rui ; Xie, Hong-Yan ; Qian, Jin-Xian ; Huang, Yan-Ni ; Yang, Fan ; Zhang, Fang-Lin ; Shao, Zhi-Ming ; Li, Da-Qiang

The molecular underpinnings behind malignant progression of breast cancer from a localized lesion to an invasive and ultimately metastatic disease are incompletely understood. Here we report that F-box only protein 22 (FBXO22) plays a dual role in mammary tumorigenesis and metastasis. FBXO22 was upregulated in primary breast tumors and promoted cell proliferation and colony formation in vitro and xenograft tumorigenicity in vivo. Surprisingly, FBXO22 suppressed epithelial-mesenchymal transition [...]

Menée à l'aide d'échantillons tumoraux prélevés sur 10 patients atteints d'un gliome, à l'aide de données du projet "The Cancer Genome Atlas", puis à l'aide d'un modèle murin, cette étude met en évidence des mécanismes de nature immunitaire par lesquels la protéine FGL2 favorise la progression tumorale

The Role of Fibrinogen-Like Protein 2 on Immunosuppression and Malignant Progression in Glioma

Latha, Khatri ; Yan, Jun ; Yang, Yuhui ; Gressot, Loyola V. ; Kong, Ling-Yuan ; Manyam, Ganiraju ; Ezhilarasan, Ravesanker ; Wang, Qianghu ; Sulman, Erik P. ; Eric Davis, R. ; Huang, Suyun ; Fuller, Gregory N. ; Rao, Arvind ; Heimberger, Amy B. ; Li, Shulin ; Rao, Ganesh

Background : Virtually all low-grade gliomas (LGGs) will progress to high-grade gliomas (HGGs), including glioblastoma, the most common malignant primary brain tumor in adults. A key regulator of immunosuppression, fibrinogen-like protein 2 (FGL2), may play an important role in the malignant transformation of LGG to HGG. We sought to determine the mechanism of FGL2 on tumor progression and to show that inhibiting FGL2 expression had a therapeutic effect. Methods : We analyzed human gliomas that [...]

Menée in vitro et in vivo sur des modèles de carcinome épidermoïde de la tête et du cou, cette étude met en évidence des mécanismes par lesquels la protéine DDX3 favorise le processus métastatique

DDX3 activates CBC-eIF3-mediated translation of uORF-containing oncogenic mRNAs to promote metastasis in HNSCC

Chen, Hung-Hsi ; Yu, Hsin- I. ; Yang, Muh-Hwa ; Tarn, Woan-Yuh

Mutated or dysregulated DDX3 participates in the progression and metastasis of cancer via its multiple roles in regulating gene expression and cellular signaling. Here we show that the high expression levels of DDX3 in head and neck squamous cell carcinoma (HNSCC) correlate with lymph node metastasis and poor prognosis and demonstrate that DDX3 is essential for the proliferation, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells. Microarray analyses revealed that DDX3 is [...]

Cet article passe en revue les travaux récents sur les mécanismes par lesquels l'augmentation des contraintes physiques s'exerçant dans les tumeurs favorise le processus invasif et réduit l'efficacité thérapeutique

Mechanisms and impact of altered tumour mechanics

Mohammadi, Hamid ; Sahai, Erik

The physical characteristics of tumours are intricately linked to the tumour phenotype and difficulties during treatment. Many factors contribute to the increased stiffness of tumours; from increased matrix deposition, matrix remodelling by forces from cancer cells and stromal fibroblasts, matrix crosslinking, increased cellularity, and the build-up of both solid and interstitial pressure. Increased stiffness then feeds back to increase tumour invasiveness and reduce therapy efficacy. Increased [...]

A partir de données issues du projet "The Cancer Genome Atlas" et à l'aide d'une méthode numérique analysant la composition du micro-environnement de tumeurs de glioblastome, cette étude identifie notamment trois sous-groupes de la maladie caractérisés par la réponse antitumorale du système immunitaire

Computational characterization of suppressive immune microenvironments in glioblastoma

Luoto, Suvi ; Hermelo, Ismaïl ; Vuorinen, Elisa M. ; Hannus, Paavo ; Kesseli, Juha ; Nykter, Matti ; Granberg, Kirsi J.

The immunosuppressive microenvironment in glioblastoma (GBM) prevents an efficient antitumoral immune response and enables tumor formation and growth. Although an understanding of the nature of immunosuppression is still largely lacking, it is important for successful cancer treatment through immune system modulation. To gain insight into immunosuppression in GBM, we performed a computational analysis to model relative immune cell content and type of immune response in each GBM tumor sample [...]