Cet article analyse le rôle de l'instabilité chromosomique dans l'initiation et le développement d'une tumeur

Chromosomal Instability in Tumor Initiation and Development

Bach, Duc-Hiep ; Zhang, Wei ; Sood, Anil K.

Chromosomal instability (CIN) is one of the major forms of genomic instability in various human cancers and is recognized as a common hallmark of tumorigenesis and heterogeneity. However, some malignant tumors show a paucity of chromosomal alterations, suggesting that tumor progression and evolution can occur in the absence of CIN. It is unclear whether CIN is stable between precursor lesions, primary tumor, and metastases or if it evolves during these steps. In this review, we describe the [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel la protéine kinase AMPK et la parkine, une ubiquitine ligase impliquée dans la maladie de Parkinson et la suppression tumorale, régulent négativement la nécroptose et la tumorigenèse induite par l'inflammation en inhibant la formation du complexe protéique RIPK1-RIPK3

The AMPK–Parkin axis negatively regulates necroptosis and tumorigenesis by inhibiting the necrosome

Lee, Seung Baek ; Kim, Jung Jin ; Han, Sang-Ah ; Fan, Yingfang ; Guo, Li-Sha ; Aziz, Khaled ; Nowsheen, Somaira ; Kim, Sung Sun ; Park, Seon-Young ; Luo, Qifeng ; Chung, Jin Ook ; Choi, Sung Il ; Aziz, Asef ; Yin, Ping ; Tong, Seo-Yun ; Fiesel, Fabienne C. ; Springer, Wolfdieter ; Zhang, Jin-San ; Lou, Zhenkun

The receptor-interacting serine/threonine-protein kinases RIPK1 and RIPK3 play important roles in necroptosis that are closely linked to the inflammatory response. Although the activation of necroptosis is well characterized, the mechanism that tunes down necroptosis is largely unknown. Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson’s disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. [...]

Menée in vitro et à l'aide de xénogreffes de tumeurs de la vessie sur des modèles murins, cette étude met en évidence un mécanisme par lequel la 5-méthylcytosine favorise la stabilisation d'ARNs messagers oncogènes et le développement de tumeurs

5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs

Chen, Xin ; Li, Ang ; Sun, Bao-Fa ; Yang, Ying ; Han, Ya-Nan ; Yuan, Xun ; Chen, Ri-Xin ; Wei, Wen-Su ; Liu, Yanchao ; Gao, Chun-Chun ; Chen, Yu-Sheng ; Zhang, MengMeng ; Ma, Xiao-Dan ; Liu, Zhuo-Wei ; Luo, Jun-Hang ; Lyu, Cong ; Wang, Hai-Lin ; Ma, Jinbiao ; Zhao, Yong-Liang ; Zhou, Fang-Jian ; Huang, Ying ; Xie, Dan ; Yang, Yun-Gui

Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C ‘reader’ recognizing m5C-modified [...]

Cet article analyse le rôle, dans la progression des tumeurs, des cellules du système immunitaire inné du micro-environnement tumoral

The Tumor Microenvironment Innately Modulates Cancer Progression

Hinshaw, Dominique C. ; Shevde, Lalita A.

Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests [...]

Menée à l'aide d'une approche bio-informatique utilisant des données d'expression génique de patients atteints d'un carcinome corticosurrénalien et menée à l'aide d'un modèle murin, cette étude met en évidence le rôle de la méthyltransférase EZH2 et du facteur de transcription E2F1 dans l'expression de gènes impliqués dans l'agressivité de la maladie

EZH2 cooperates with E2F1 to stimulate expression of genes involved in adrenocortical carcinoma aggressiveness

Tabbal, Houda ; Septier, Amandine ; Mathieu, Mickael ; Drelon, Coralie ; Rodriguez, Stephanie ; Djari, Cyril ; Batisse-Lignier, Marie ; Tauveron, Igor ; Pointud, Jean-Christophe ; Sahut-Barnola, Isabelle ; Ragazzon, Bruno ; Assie, Guillaume ; Bertherat, Jérôme ; Lefrançois-Martinez, Anne-Marie ; Martinez, Antoine ; Val, Pierre

Background : EZH2 is overexpressed and associated with poor prognosis in adrenocortical carcinoma (ACC) and its inhibition reduces growth and aggressiveness of ACC cells in culture. Although EZH2 was identified as the methyltransferase that deposits the repressive H3K27me3 histone mark, it can cooperate with transcription factors to stimulate gene transcription. Methods : We used bioinformatics approaches on gene expression data from three cohorts of patients and a mouse model of EZH2 ablation, [...]

Menée in vitro et à l'aide d'un modèle murin de myélome, cette étude met en évidence un mécanisme par lequel le niveau d'expression de CD 138 à la surface des cellules cancéreuses régule de façon dynamique la transition entre la phase de croissance et la phase de dissémination

Dynamic CD138 surface expression regulates switch between myeloma growth and dissemination

Akhmetzyanova, Ilseyar ; McCarron, Mark J. ; Parekh, Samir ; Chesi, Marta ; Bergsagel, P. Leif ; Fooksman, David R.

The canonical plasma cell marker CD138 (syndecan-1) is highly expressed on the myeloma cell surface, but its functional role in vivo is unclear, as well as the ontogeny of CD138-high and CD138-negative (neg) myeloma cells. In this study we used an in vivo murine Vk*MYC myeloma model where CD138 is heterogeneously expressed depending on tumor size. We find that in comparison to CD138-neg myeloma cells, the CD138-high subset of myeloma cells is highly proliferative, less apoptotic, and enhanced [...]

Menée sur des lignées cellulaires de myélome multiple humain et à l'aide d'une xénogreffe sur un modèle murin, cette étude met en évidence un mécanisme par lequel la forme soluble de la glycoprotéine SLAMF7 favorise la croissance des cellules cancéreuses en interagissant avec la forme membranaire de SLAMF7

Soluble SLAMF7 promotes the growth of myeloma cells via homophilic interaction with surface SLAMF7

Kikuchi, Jiro ; Hori, Mitsuo ; Iha, Hidekatsu ; Toyama-Sorimachi, Noriko ; Hagiwara, Shotaro ; Kuroda, Yoshiaki ; Koyama, Daisuke ; Izumi, Tohru ; Yasui, Hiroshi ; Suzuki, Atsushi ; Furukawa, Yusuke

SLAMF7 is expressed mainly on multiple myeloma (MM) cells and considered an ideal target for immunotherapeutic approaches. Indeed, elotuzumab, an anti-SLAMF7 antibody, is used for the treatment of MM in combination with immunomodulatory drugs. SLAMF7 is cleaved via unknown mechanisms and detected as a soluble form (sSLAMF7) exclusively in the serum of MM patients; however, little is known about the role of sSLAMF7 in MM biology. In this study, we found that sSLAMF7 enhanced the growth of MM [...]

Menée in vitro puis à l'aide d'un modèle murin et d'une modélisation, cette étude met en évidence un mécanisme par lequel l'acidité intratumorale favorise la progression des tumeurs prostatiques en altérant le phénotype des macrophages

Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer

El-Kenawi, Asmaa ; Gatenbee, Chandler ; Robertson-Tessi, Mark ; Bravo, Rafael ; Dhillon, Jasreman ; Balagurunathan, Yoganand ; Berglund, Anders ; Visvakarma, Naveen ; Ibrahim-Hashim, Arig ; Choi, Jung ; Luddy, Kimberly ; Gatenby, Robert ; Pilon-Thomas, Shari ; Anderson, Alexander ; Ruffell, Brian ; Gillies, Robert

Background : Tumours rapidly ferment glucose to lactic acid even in the presence of oxygen, and coupling high glycolysis with poor perfusion leads to extracellular acidification. We hypothesise that acidity, independent from lactate, can augment the pro-tumour phenotype of macrophages. Methods : We analysed publicly available data of human prostate cancer for linear correlation between macrophage markers and glycolysis genes. We used zwitterionic buffers to adjust the pH in series of in vitro [...]

Menée à l'aide de xénogreffes de cancer mammaire sur un modèle murin, cette étude met en évidence un mécanisme par lequel la coopération de différentes sous-populations de cellules tumorales favorise le processus métastatique en agissant sur le micro-environnement immunitaire local et à distance sur les cellules souches mésenchymateuses de la moelle osseuse

Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments

Janiszewska, Michalina ; Tabassum, Doris P. ; Castaño, Zafira ; Cristea, Simona ; Yamamoto, Kimiyo N. ; Kingston, Natalie L. ; Murphy, Katherine C. ; Shu, Shaokun ; Harper, Nicholas W. ; Del Alcazar, Carlos Gil ; Aleckovic, Masa ; Ekram, Muhammad B. ; Cohen, Ofir ; Kwak, Minsuk ; Qin, Yuanbo ; Laszewski, Tyler ; Luoma, Adrienne ; Marusyk, Andriy ; Wucherpfennig, Kai W. ; Wagle, Nikhil ; Fan, Rong ; Michor, Franziska ; McAllister, Sandra S. ; Polyak, Kornelia

Most human tumours are heterogeneous, composed of cellular clones with different properties present at variable frequencies. Highly heterogeneous tumours have poor clinical outcomes, yet the underlying mechanism remains poorly understood. Here, we show that minor subclones of breast cancer cells expressing IL11 and FIGF (VEGFD) cooperate to promote metastatic progression and generate polyclonal metastases composed of driver and neutral subclones. Expression profiling of the epithelial and [...]