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Journal Cancer Res.

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The Fire Within: NF-κB involvement in Non-Small Cell Lung Cancer.

Foteinos-Ioannis D Dimitrakopoulos, Anastasia E Kottorou, Melpomeni Kalofonou, Haralabos P Kalofonos,

Thirty-four years since its discovery, nuclear factor kappa B (NF-κB) remains a transcription factor with great potential for cancer therapy. However, NF-κB-targeted therapies have yet to find a way to be clinically translatable. Here we focus exclusively on the role of NF-κB in non-small cell lung cancer (NSCLC) and discuss ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Y Chromosome LncRNA are involved in Radiation Response of Male Non-Small Cell Lung Cancer Cells.

Tayvia Brownmiller, Jamie A Juric, Abby D Ivey, Brandon M Harvey, Emily S Westemeier, Michael T Winters, Alyson M Stevens, Alana N Stanley, Karen E Hayes, Samuel A Sprowls, Amanda S Gatesman Ammer, Mackenzee Walker, Erik A Bey, Xiaoliang Wu, Zuan-Fu Lim, Lin Zhu, Sijin Wen, Gangqing Hu, Patrick C Ma, Ivan Martinez,

Numerous studies have implicated changes in the Y chromosome in male cancers, yet few have investigated the biological importance of Y chromosome non-coding RNA. Here we identify a group of Y chromosome-expressed long non-coding RNA (lncRNA) that are involved in male non-small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive male ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Not Black or White but Shades of Gray: Homologous Recombination Deficiency as a Continuous Variable Modulated by RNF168.

Lin Wang, Gerburg M Wulf,

In this issue of Cancer Research, the study by Krais and colleagues underscores that DNA damage repair by homologous recombination (HR) is not an all-or-nothing phenomenon, but that HR competency comes on a spectrum, ranging from complete deficiency to proficiency. Residual low-level HR in BRCA1-mutant cancer cells turns out to ... Read more >>

Cancer Res. (Cancer research)
[2020, 80(13):2720-2721]

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When the Smoke Clears m6A from a Y Chromosome-Linked lncRNA, Men Get an Increased Risk of Cancer.

A Rouf Banday, Brenen W Papenberg, Ludmila Prokunina-Olsson,

Long noncoding RNAs (lncRNA) have been implicated in many diseases, including cancer. Although these disease-associated effects have been mostly attributed to the ability of lncRNAs to function as regulatory noncoding transcripts, there is growing evidence that lncRNAs may also encode functional micropeptides. In the current issue of Cancer Research, Wu ... Read more >>

Cancer Res. (Cancer research)
[2020, 80(13):2718-2719]

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Highlights from Recent Cancer Literature.

Cancer Res. (Cancer research)
[2020, 80(13):2703-2704]

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Cancer-associated point mutations in the DLC1 tumor suppressor and other Rho-GAPs occur frequently and are associated with decreased function.

Dunrui Wang, Xiaolan Qian, Beatriz Sanchez-Solana, Brajendra K Tripathi, Marian E Durkin, Douglas R Lowy,

In advanced cancer, the RHOA GTPase is often active together with reduced expression of genes encoding Rho-specific GTPase-accelerating proteins (Rho-GAP), which negatively regulate RHOA and related GTPases. Here we used the TCGA dataset to examine 12 tumor types (including colon, breast, prostate, pancreas, lung adenocarcinoma and squamous cell carcinoma) for ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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HDAC6 plays a non-canonical role in the regulation of anti-tumor immune responses, dissemination, and invasiveness of breast cancer.

Debarati Banik, Satish Noonepalle, Melissa Hadley, Erica Palmer, Maria Gracia-Hernandez, Christian Zevallos-Delgado, Namratta Manhas, Hayk Simonyan, Colin N Young, Anastas Popratiloff, Katherine B Chiappinelli, Rohan Fernandes, Eduardo M Sotomayor, Alejandro Villagra,

Despite the outstanding clinical results of immune checkpoint blockade (ICB) in melanoma and other cancers, clinical trials in breast cancer have reported low responses to these therapies. Current efforts are now focused on improving the treatment efficacy of ICB in breast cancer using new combination designs such as molecularly targeted ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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FTO-Dependent N6-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling.

Hao Huang, Yinu Wang, Manoj Kandpal, Guangyuan Zhao, Horacio Cardenas, Yanrong Ji, Anusha Chaparala, Edward J Tanner, Jianjun Chen, Ramana V Davuluri, Daniela Matei,

N6-Methyladenosine (m6A) is the most abundant modification of mammalian messenger RNAs (mRNA). RNA methylation fine tunes RNA stability and translation, altering cell fate. The fat mass- and obesity-associated protein (FTO) is an m6A demethylase with oncogenic properties in leukemia. Here we show that FTO expression is suppressed in ovarian tumors ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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CXCR4 in tumor epithelial cells mediates desmoplastic reaction in pancreatic ductal adenocarcinoma.

Toshihiro Morita, Yuzo Kodama, Masahiro Shiokawa, Katsutoshi Kuriyama, Saiko Marui, Takeshi Kuwada, Yuko Sogabe, Tomoaki Matsumori, Nobuyuki Kakiuchi, Teruko Tomono, Atsushi Mima, Tatsuki Ueda, Motoyuki Tsuda, Yuki Yamauchi, Yoshihiro Nishikawa, Yojiro Sakuma, Yuji Ota, Takahisa Maruno, Norimitsu Uza, Takashi Nagasawa, Tsutomu Chiba, Hiroshi Seno,

Pancreatic ductal adenocarcinoma (PDAC) features abundant stromal cells with an excessive extracellular matrix (ECM), termed the desmoplastic reaction. CXCR4 is a cytokine receptor for stromal cell-derived factor-1 (CXCL12) expressed in PDAC, but its roles in PDAC and the characteristic desmoplastic reaction remain unclear. Here we generated a mouse model of ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Palmitoylated proteins on AML-derived extracellular vesicles promote myeloid-derived suppressor cell differentiation via TLR2/Akt/mTOR signaling.

Sehmus Tohumeken, Rebecca Baur, Martin Böttcher, Andrej Stoll, Romy Loschinski, Konstantinos Panagiotidis, Martina Braun, Domenica Saul, Simon Völkl, Andreas S Baur, Heiko Bruns, Andreas Mackensen, Regina Jitschin, Dimitrios Mougiakakos,

Acute myeloid leukemia (AML) represents the most common acute leukemia amongst adults. Despite recent progress in diagnosis and treatment, long-term outcome remains unsatisfactory. The success of allogeneic stem cell transplantation underscores the immunoresponsive nature of AML creating the basis for further exploiting immunotherapies. However, emerging evidence suggests that AML, similar ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Traditional Diagnostics versus Disruptive Technology: The role of the pathologist in the era of liquid biopsy.

Lynette M Sholl, Geoffrey R Oxnard, Cloud P Paweletz,

Precision medicine in cancer care is predicated on access to several fundamental pieces of data: (1) a precise tumor diagnosis, (2) accurate stage classification, and (3) protein or molecular biomarkers that predict efficacy of targeted therapies. For all cancer patients, these data points are generated by obtaining a tumor sample ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Lymphatic vessels in tumor dissemination vs. immunotherapy.

Kari Vaahtomeri, Kari Alitalo,

During the growth of various cancers, primary tumors can escape anti-tumor immune responses of their host and eventually disseminate into distant organs. Peritumoral lymphatic vessels connect the primary tumor to lymph nodes, facilitating tumor entry into lymph nodes, systemic circulation, and metastasis. Lymph node metastases that occur frequently provide sites ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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LDtrait: an online tool for identifying published phenotype associations in linkage disequilibrium.

Shu-Hong Lin, Derek W Brown, Mitchell J Machiela,

Genome-wide association studies (GWAS) have identified thousands of germline susceptibility loci associated with risk for cancer as well as a wide range of other traits and diseases. An interest of many investigators is identifying traits or diseases that share common susceptibility loci. We developed LDtrait (https://ldlink.nci.nih.gov/?tab=ldtrait) as an open access ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Obesity/type 2 diabetes-associated liver tumors are sensitive to Cyclin D1 deficiency.

Chi Luo, Jiaxin Liang, Kfir Sharabi, Maximilian Hatting, Elizabeth A Perry, Clint Dj Tavares, Lipika Goyal, Amitabh Srivastava, Marc Bilodeau, Andrew X Zhu, Piotr Sicinski, Pere Puigserver,

Type 2 diabetes, which is mainly linked to obesity, is associated with increased incidence of liver cancer. We have previously found that in various models of obesity/diabetes, hyperinsulinemia maintains heightened hepatic expression of Cyclin D1, suggesting a plausible mechanism linking diabetes and liver cancer progression. Here we show that Cyclin ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Extracellular vesicles from cancer-associated fibroblasts containing annexin A6 induces FAK-YAP activation by stabilizing β1 integrin, enhancing drug resistance.

Tomoyuki Uchihara, Keisuke Miyake, Atsuko Yonemura, Yoshihiro Komohara, Rumi Itoyama, Mayu Koiwa, Tadahito Yasuda, Kota Arima, Kazuto Harada, Kojiro Eto, Hiromitsu Hayashi, Masaaki Iwatsuki, Shiro Iwagami, Yoshifumi Baba, Naoya Yoshida, Masakazu Yashiro, Mari Masuda, Jaffer A Ajani, Patrick Tan, Hideo Baba, Takatsugu Ishimoto,

Extracellular vesicles (EV) from cancer-associated fibroblasts (CAF) are composed of diverse payloads. Although CAF impact the aggressive characteristics of gastric cancer (GC) cells, the contribution of CAF-EV to GC progression has not been elucidated. Here we investigated the molecular mechanism of the changes in GC characteristics induced by CAF-EV. CAF ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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MR Imaging Distinguishes Tumor Hypoxia Levels of Different Prognostic and Biological Significance in Cervical Cancer.

Tiril Hillestad, Tord Hompland, Christina S Fjeldbo, Vilde E Skingen, Unn Beate Salberg, Eva-Katrine Aarnes, Anja Nilsen, Kjersti V Lund, Tina S Evensen, Gunnar B Kristensen, Trond Stokke, Heidi Lyng,

Tumor hypoxia levels range from mild to severe and have different biological and therapeutical consequences but are not easily assessable in patients. Here we present a method based on diagnostic dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) that reflects a continuous range of hypoxia levels in tumors of cervical ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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KRASQ61H preferentially signals through MAPK in a RAF dimer-dependent manner in non-small cell lung cancer.

Zhi-Wei Zhou, Chiara Ambrogio, Asim K Bera, Qing Li, Xing-Xiao Li, Lianbo Li, Jieun Son, Sudershan Gondi, Jiaqi Li, Emily Campbell, Hua Jin, Jeffrey J Okoro, Cheng-Xiong Xu, Pasi A Janne, Kenneth D Westover,

Assembly of RAS molecules into complexes at the cell membrane is critical for RAS signaling. We previously showed that oncogenic KRAS codon 61 mutations increase its affinity for RAF, raising the possibility that KRASQ61H, the most common KRAS mutation at codon 61, upregulates RAS signaling through mechanisms at the level ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Noninvasive MRI native T1 mapping detects response to MYCN-targeted therapies in the Th-MYCN model of neuroblastoma.

Konstantinos Zormpas-Petridis, Evon Poon, Matthew Clarke, Neil P Jerome, Jessica K R Boult, Matthew D Blackledge, Fernando Carceller, Alexander Koers, Giuseppe Barone, Andrew D J Pearson, Lucas Moreno, John Anderson, Neil Sebire, Kieran McHugh, Dow-Mu Koh, Louis Chesler, Yinyin Yuan, Simon P Robinson, Yann Jamin,

Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies in neural crest development. Therapeutic approaches aiming to destabilize MYCN protein, such as small molecule inhibitors of Aurora ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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YAP Enhances Tumor Cell Dissemination by Promoting Intravascular Motility and Re-entry into Systemic Circulation.

David C Benjamin, Joon Ho Kang, Bashar Hamza, Emily M King, John M Lamar, Scott R Manalis, Richard O Hynes,

The oncogene YAP has been shown previously to promote tumor growth and metastasis. However, how YAP influences the behavior of tumor cells traveling within the circulatory system has not been as well explored. Given that rate-limiting steps of metastasis are known to occur while tumor cells enter, travel through, or ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Rb and p53 execute distinct roles in the development of pancreatic neuroendocrine tumors.

Yuki Yamauchi, Yuzo Kodama, Masahiro Shiokawa, Nobuyuki Kakiuchi, Saiko Marui, Takeshi Kuwada, Yuko Sogabe, Teruko Tomono, Atsushi Mima, Toshihiro Morita, Tomoaki Matsumori, Tatsuki Ueda, Motoyuki Tsuda, Yoshihiro Nishikawa, Katsutoshi Kuriyama, Yojiro Sakuma, Yuji Ota, Takahisa Maruno, Norimitsu Uza, Atsuhiro Masuda, Hisato Tatsuoka, Daisuke Yabe, Sachiko Minamiguchi, Toshihiko Masui, Nobuya Inagaki, Shinji Uemoto, Tsutomu Chiba, Hiroshi Seno,

Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1-3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Interaction with CD68 and regulation of GAS6 expression by endosialin in fibroblasts drives recruitment and polarization of macrophages in hepatocellular carcinoma.

Fa Yang, Yan Wei, Donghui Han, Yu Li, Shengjia Shi, Dian Jiao, Jieheng Wu, Qiang Zhang, Changhong Shi, Lijun Yang, Wei Song, Jingliang Zhang, Yueheng Han, Rui Zhang, An-Gang Yang, Dimiter S Dimitrov, Aizhi Zhao, Weijun Qin, Weihong Wen,

Fibroblasts and macrophages play key roles in the development of hepatocellular carcinoma (HCC). However, crosstalk between these two kinds of cells has not been well-studied. Endosialin (CD248/TEM1) is a transmembrane glycoprotein that is expressed in certain cancer cells, tumor stromal cells, and pericytes. In this study, we found that endosialin ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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A Pygopus 2-histone interaction is critical for cancer cell de-differentiation and progression in malignant breast cancer.

Meera Saxena, Ravi K R Kalathur, Natalia Rubinstein, Andrea Vettiger, Nami Sugiyama, Melanie Neutzner, Mairene Coto-Llerena, Venkatesh Kancherla, Caner Ercan, Salvatore Piscuoglio, Jonas Fischer, Ernesta Fagiani, Claudio Cantù, Konrad Basler, Gerhard Christofori,

Pygopus 2 (Pygo2) is a co-activator of Wnt/β-catenin signaling that can bind bi- or trimethylated lysine 4 of histone-3 (H3K4me2/3) and participate in chromatin reading and writing. It remains unknown whether the Pygo2- H3K4me2/3 association has a functional relevance in breast cancer progression in vivo. To investigate the functional relevance ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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Platelet-specific PDGFB ablation impairs tumor vessel integrity and promotes metastasis.

Yanyu Zhang, Jessica Cedervall, Anahita Hamidi, Melanie Herre, Kati Viitaniemi, Gabriela D'Amico, Zuoxiu Miao, Ragaseema Valsala Madhavan Unnithan, Alessandra Vaccaro, Luuk van Hooren, Maria Georganaki, Åsa Thulin, Qi Qiao, Johanna Andrae, Agneta Siegbahn, Carl-Henrik Heldin, Kari Alitalo, Christer Betsholtz, Anna Dimberg, Anna-Karin Olsson,

Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor beta (PDGFRbeta)-positive pericytes to blood vessels. The endothelium is an essential source of PDGFB in this process. Platelets constitute a major reservoir of PDGFB and are continuously activated in the tumor microenvironment, exposing tumors to the ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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NRAS status determines sensitivity to SHP2 inhibitor combination therapies targeting the RAS-MAPK pathway in neuroblastoma.

Ivette Valencia-Sama, Yagnesh Ladumor, Lynn Kee, Teresa Adderley, Gabriella Christopher, Claire M Robinson, Yoshihito Kano, Michael Ohh, Meredith S Irwin,

Survival for high-risk neuroblastoma (NB) remains poor and treatment for relapsed disease rarely leads to long-term cures. Large sequencing studies of NB tumors from diagnosis have not identified common targetable driver mutations other than the 10% of tumors that harbor mutations in the anaplastic lymphoma kinase (ALK) gene. However, at ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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p38gamma MAPK is essential for aerobic glycolysis and pancreatic tumorigenesis.

Fang Wang, Xiao-Mei Qi, Ryan Wertz, Matthew Mortensen, Catherine Hagen, John Evans, Yuri Sheinin, Michael James, Pengyuan Liu, Susan Tsai, James Thomas, Alexander Mackinnon, Michael Dwinell, Charles R Myers, Ramon Bartrons, Liwu Fu, Guan Chen,

KRAS is mutated in most pancreatic ductal adenocarcinomas (PDAC) and yet remains undruggable. Here we report that p38gamma MAPK, which promotes PDAC tumorigenesis by linking KRAS signaling and aerobic glycolysis (also called the Warburg effect), is a novel therapeutic target. p38gamma interacted with a glycolytic activator PFKFB3 that was dependent ... Read more >>

Cancer Res. (Cancer research)
[2020, :]

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