Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en augmentant la tolérance des cellules cancéreuses au stress oxydant, le canal ionique TRPA1 favorise la croissance tumorale

Cancer Cells Co-opt the Neuronal Redox-Sensing Channel TRPA1 to Promote Oxidative-Stress Tolerance

Takahashi, Nobuaki ; Chen, Hsing-Yu ; Harris, Isaac S. ; Stover, Daniel G. ; Selfors, Laura M. ; Bronson, Roderick T. ; Deraedt, Thomas ; Cichowski, Karen ; Welm, Alana L. ; Mori, Yasuo ; Mills, Gordon B. ; Brugge, Joan S.

Cancer cell survival is dependent on oxidative-stress defenses against reactive oxygen species (ROS) that accumulate during tumorigenesis. Here, we show a non-canonical oxidative-stress defense mechanism through TRPA1, a neuronal redox-sensing Ca2+-influx channel. In TRPA1-enriched breast and lung cancer spheroids, TRPA1 is critical for survival of inner cells that exhibit ROS accumulation. Moreover, TRPA1 promotes resistance to ROS-producing chemotherapies, and TRPA1 inhibition suppresses [...]

Menée sur des lignées cellulaires cancéreuses et à l'aide de xénogreffes sur des modèles murins, cette étude met en évidence des mécanismes par lesquels la protéine EYA favorise l'angiogenèse et la croissance tumorale

The protein tyrosine phosphatase activity of Eyes Absent contributes to tumor angiogenesis and tumor growth

Wang, Yuhua ; Pandey, Ram Naresh ; Riffle, Stephen ; Chintala, Hemabindu ; Wikenheiser-Brokamp, Kathryn A. ; Hegde, Rashmi S.

DNA damage repair capacity is required for cells to survive catastrophic DNA damage and proliferate under conditions of intra-tumoral stress. The ability of the minor histone protein H2AX to serve as a hub for the assembly of a productive DNA damage repair complex is a necessary step in preventing DNA damage-induced cell death. The Eyes Absent (EYA) proteins dephosphorylate the terminal tyrosine residue of H2AX thus permitting assembly of a productive DNA repair complex. Here we use genetic and [...]

Menée in vivo, cette étude met en évidence des mécanismes par lesquels la protéine SHP2 favorise la croissance tumorale d'un cancer du poumon non à petites cellules présentant un gène KRAS muté

SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo

Mainardi, Sara ; Mulero-Sánchez, Antonio ; Prahallad, Anirudh ; Germano, Giovanni ; Bosma, Astrid ; Krimpenfort, Paul ; Lieftink, Cor ; Steinberg, Jeffrey D. ; de Wit, Niels ; Gonçalves-Ribeiro, Samuel ; Nadal, Ernest ; Bardelli, Alberto ; Villanueva, Alberto ; Bernards, Rene

RAS mutations are frequent in human cancer, especially in pancreatic, colorectal and non-small-cell lung cancers (NSCLCs)1–3. Inhibition of the RAS oncoproteins has proven difficult 4 , and attempts to target downstream effectors5–7 have been hampered by the activation of compensatory resistance mechanisms 8 . It is also well established that KRAS-mutant tumors are insensitive to inhibition of upstream growth factor receptor signaling. Thus, epidermal growth factor receptor antibody therapy is [...]

Menée sur des lignées cellulaires de sarcome synovial, cette étude met en évidence des mécanismes par lesquels la protéine de fusion SS18-SSX favorise la prolifération des cellules cancéreuses

The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma

McBride, Matthew J. ; Pulice, John L. ; Beird, Hannah C. ; Ingram, Davis R. ; D’Avino, Andrew R. ; Shern, Jack F. ; Charville, Gregory W. ; Hornick, Jason L. ; Nakayama, Robert T. ; Garcia-Rivera, Enrique M. ; Araujo, Dejka M. ; Wang, Wei-Lien ; Tsai, Jen-Wei ; Yeagley, Michelle ; Wagner, Andrew J. ; Futreal, P. Andrew ; Khan, Javed ; Lazar, Alexander J. ; Kadoch, Cigall

Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated [...]

Menée in vitro et in vivo sur des modèles de carcinome hépatocellulaire, cette étude met en évidence des mécanismes par lesquels, en augmentant l'expression de la protéine Vimentin, le facteur de transcription Twist1 favorise la transition épithélio-mésenchymateuse

Twist1 regulates Vimentin through Cul2 circular RNA to promote EMT in hepatocellular carcinoma

Meng, Jing ; Chen, Shuang ; Han, Jingxia ; Qian, Baoxin ; Wang, Xiaorui ; Zhong, Weilong ; Qin, Yuan ; Zhang, Heng ; Gao, Wanfeng ; Lei, Yueyang ; Yang, Wei ; Yang, Lan ; Zhang, Chao ; Liu, Huijuan ; Liu, Yanrong ; Zhou, Hong-gang ; Sun, Tao ; Yang, Cheng

Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of Vimentin. How Twist1 regulates this expression remains unclear. Here we report that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of Vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, [...]

Basée sur les concepts de l'ingéniérie écologique, cette étude présente un modèle mathématique rendant compte de la construction d'une niche prémétastatique et permettant d'expliquer pourquoi la majorité des métastases sont issues de cellules cancéreuses porteuses de mutations apparues de façon précoce dans la tumeur primitive

Competition and niche construction in a model of cancer metastasis

Qian, Jimmy J. ; Akçay, Erol

Niche construction theory states that not only does the environment act on populations to generate Darwinian selection, but organisms reciprocally modify the environment and the sources of natural selection. Cancer cells participate in niche construction as they alter their microenvironments and create pre-metastatic niches; in fact, metastasis is a product of niche construction. Here, we present a mathematical model of niche construction and metastasis. Our model contains producers, which pay [...]

Menée in vitro, cette étude met en évidence des mécanismes par lesquels, en régulant l'expression de la protéine ITGB3, l'enzyme ADAR1 réprime le processus invasif

ADAR1-mediated regulation of melanoma invasion

Nemlich, Yael ; Baruch, Erez Nissim ; Besser, Michal Judith ; Shoshan, Einav ; Bar-Eli, Menashe ; Anafi, Liat ; Barshack, Iris ; Schachter, Jacob ; Ortenberg, Rona ; Markel, Gal

Melanoma cells use different migratory strategies to exit the primary tumor mass and invade surrounding and subsequently distant tissues. We reported previously that ADAR1 expression is downregulated in metastatic melanoma, thereby facilitating proliferation. Here we show that ADAR1 silencing enhances melanoma cell invasiveness and ITGB3 expression. The enhanced invasion is reversed when ITGB3 is blocked with antibodies. Re-expression of wild-type or catalytically inactive ADAR1 establishes [...]

Menée à l'aide de modèles murins de cancer métastatique de la prostate, cette étude met en évidence des mécanismes par lesquels, en régulant l'expression de l'oncoprotéine STMN1, le micro-ARN miR-34a favorise la progression tumorale

miR-34a Regulates Expression of the Stathmin-1 Oncoprotein and Prostate Cancer Progression

Chakravarthi, Balabhadrapatruni V. S. K. ; Chandrashekar, Darshan S. ; Agarwal, Sumit ; Balasubramanya, Sai Akshaya Hodigere ; Pathi, Satya S. ; Goswami, Moloy T. ; Jing, Xiaojun ; Wang, Rui ; Mehra, Rohit ; Asangani, Irfan A. ; Chinnaiyan, Arul M. ; Manne, Upender ; Sonpavde, Guru ; Netto, George J. ; Gordetsky, Jennifer ; Varambally, Sooryanarayana

In aggressive prostate cancers, the oncoprotein STMN1 (also known as stathmin 1 and oncoprotein 18) is often overexpressed. STMN1 is involved in various cellular processes, including cell proliferation, motility, and tumor metastasis. Here, it was found that the expression of STMN1 RNA and protein is elevated in metastatic prostate cancers. Knockdown of STMN1 resulted in reduced proliferation and invasion of cells and tumor growth and metastasis in vivo. Furthermore, miR-34a downregulated STMN1 [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, via la protéine du récepteur des androgènes, un long ARN non codant (ARLNC1) favorise la progression d'une tumeur de la prostate

Analysis of the androgen receptor–regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression

Zhang, Yajia ; Pitchiaya, Sethuramasundaram ; Cieslik, Marcin ; Niknafs, Yashar S. ; Tien, Jean C. Y. ; Hosono, Yasuyuki ; Iyer, Matthew K. ; Yazdani, Sahr ; Subramaniam, Shruthi ; Shukla, Sudhanshu K. ; Jiang, Xia ; Wang, Lisha ; Liu, Tzu-Ying ; Uhl, Michael ; Gawronski, Alexander R. ; Qiao, Yuanyuan ; Xiao, Lanbo ; Dhanasekaran, Saravana M. ; Juckette, Kristin M. ; Kunju, Lakshmi P. ; Cao, Xuhong ; Patel, Utsav ; Batish, Mona ; Shukla, Girish C. ; Paulsen, Michelle T. ; Ljungman, Mats ; Jiang, Hui ; Mehra, Rohit ; Backofen, Rolf ; Sahinalp, Cenk S. ; Freier, Susan M. ; Watt, Andrew T. ; Guo, Shuling ; Wei, John T. ; Feng, Felix Y. ; Malik, Rohit ; Chinnaiyan, Arul M.

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA–RNA interaction. ARLNC1 [...]

Cet article passe en revue les travaux récents sur les mécanismes par lesquels des voies de signalisation liées aux cils des cellules cancéreuses et des cellules du microenvironnement tumoral interviennent dans la croissance tumorale et la réponse thérapeutique

Ciliary signalling in cancer

Liu, Hanqing ; Kiseleva, Anna A. ; Golemis, Erica A.

Although tumours initiate from oncogenic changes in a cancer cell, subsequent tumour progression and therapeutic response depend on interactions between the cancer cells and the tumour microenvironment (TME). The primary monocilium, or cilium, provides a spatially localized platform for signalling by Hedgehog, Notch, WNT and some receptor tyrosine kinase pathways and mechanosensation. Changes in ciliation of cancer cells and/or cells of the TME during tumour development enforce asymmetric [...]

Cet article passe en revue les travaux récents ayant identifié les cellules à l'origine du développement d'un carcinome épidermoïde dans divers organes

Deciphering the cells of origin of squamous cell carcinomas

Sánchez-Danés, Adriana ; Blanpain, Cedric

Squamous cell carcinomas (SCCs) are among the most prevalent human cancers. SCC comprises a wide range of tumours originated from diverse anatomical locations that share common genetic mutations and expression of squamous differentiation markers. SCCs arise from squamous and non-squamous epithelial tissues. Here, we discuss the different studies in which the cell of origin of SCCs has been uncovered by expressing oncogenes and/or deleting tumour suppressor genes in the different cell lineages [...]