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JOURNAL ARTICLE
Jonathan Sussman, Nathalia Y Kim, Samantha B Kemp, Daniel Traum, Takeshi Katsuda, Benjamin M Kahn, Jason Xu, Il-Kyu Kim, Cody Eskandarian, Devora Delman, Gregory L Beatty, Klaus H Kaestner, Amber L Simpson, Ben Z Stanger
Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) is driven by complex interactions between the neoplastic component and the tumor microenvironment (TME), which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy. Characterization of the spatial features of the vascular niche could advance our understanding of inter- and intra-tumoral heterogeneity in PDAC...
May 2, 2024: Cancer Research
#2
JOURNAL ARTICLE
Kevin A MacPherson-Hawthorne, Rosalie C Sears
MYC is an oncogenic transcription factor that binds gene promoters to facilitate oncogenic gene expression. When overexpressed, as is the case in most human cancers, MYC also invades active enhancers-cis-regulatory elements that are critical for regulating gene expression. In previous studies, the regulatory significance of MYC enhancer invasion in cancer cells has been debated. In their study published in Nature Genetics, Jakobsen and colleagues establish a new role for MYC at enhancer regions: regulating cancer type-specific gene programs...
May 2, 2024: Cancer Research
#3
JOURNAL ARTICLE
Jie Xia, Lixing Zhang, Xilei Peng, Juchuanli Tu, Siqin Li, Xueyan He, Fengkai Li, Jiankun Qiang, Haonan Dong, Qiaodan Deng, Cuicui Liu, Jiahui Xu, Rui Zhang, Quentin Liu, Guohong Hu, Chong Liu, Yi-Zhou Jiang, Zhi-Ming Shao, Ceshi Chen, Suling Liu
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Interleukin-1 receptor type 2 (IL1R2) promotes breast tumor-initiating cell (BTIC) self-renewal and tumor growth in TNBC, indicating that targeting it could improve patient treatment. Here, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of tumor-associated macrophages (TAMs) to inhibit BTIC self-renewal and CD8+ T cell exhaustion, which resulted in reduced tumor burden and prolonged survival in TNBC mouse models...
April 24, 2024: Cancer Research
#4
JOURNAL ARTICLE
Ewa Sicinska, Vijaya Sudhakara Rao Kola, Joseph A Kerfoot, Madeleine L Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J Church, Esther Landesman-Bollag, Yosef Landesman, Matthew L Hemming
Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion. A better understanding of the mechanisms by which this oncogenic transcriptional regulator drives cancer growth is needed to help identify potential therapeutic targets. Here, we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models, identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology...
April 24, 2024: Cancer Research
#5
JOURNAL ARTICLE
Sheng Yang, Dongsheng Zhang, Qingyang Sun, Hongxu Nie, Yue Zhang, Xiaowei Wang, Yuanjian Huang, Yueming Sun
Colorectal cancer (CRC) is one of the most common malignant tumors in humans, with liver metastasis being the primary cause of mortality. The epithelial-mesenchymal transition (EMT) process endows cancer cells with enhanced metastatic potential. To elucidate the cellular mechanisms driving EMT in CRC, we analyzed single-cell RNA-sequencing (scRNA-seq) data from 11 non-metastatic primary tumors (TnM) and 11 metastatic primary tumors (TM) from CRC patients. Compared to TnM group, the TM samples showed elevated numbers of malignant epithelial cell and cancer-associated fibroblast (CAF) subsets that displayed enrichments of EMT, angiogenesis, and TGF-β signaling pathways...
April 24, 2024: Cancer Research
#6
JOURNAL ARTICLE
Raj Kumar Shrestha, Zeyad D Nassar, Adrienne R Hanson, Richard Iggo, Scott L Townley, Jonas Dehairs, Chui Yan Mah, Madison Helm, Mohammadreza Alizadeh-Ghodsi, Marie Pickering, Bart Ghesquiere, Matthew J Watt, Lake-Ee Quek, Andrew J Hoy, Wayne D Tilley, Johannes V Swinnen, Lisa M Butler, Luke A Selth
Solid tumors are highly reliant on lipids for energy, growth, and survival. In prostate cancer, the activity of the androgen receptor (AR) is associated with reprogramming of lipid metabolic processes. Here, we identified acyl-CoA synthetase medium chain family members 1 and 3 (ACSM1 and ACSM3) as AR-regulated mediators of prostate cancer metabolism and growth. ACSM1 and ACSM3 were upregulated in prostate tumors compared to non-malignant tissues and other cancer types. Both enzymes enhanced proliferation and protected prostate cancer cells from death in vitro, while silencing ACSM3 led to reduced tumor growth in an orthotopic xenograft model...
April 24, 2024: Cancer Research
#7
JOURNAL ARTICLE
Jose A Enríquez, María Mittelbrunn
Tumor cells rewire their metabolism to fulfill the demands of highly proliferative cells. This changes cellular metabolism to adapt to fuel and oxygen availability for energy production and to increase the synthesis capacity of building blocks for cell division and growth. In addition, the metabolic shift also modulates the immunogenicity of the tumor cells. Recently, Mahmood and colleagues reported a connection between mitochondrial DNA mutations in cancer cells and their response to immunotherapy in a mouse model of melanoma...
April 24, 2024: Cancer Research
#8
JOURNAL ARTICLE
Jorg Dietrich, Michael W Parsons, Emiliano Santarnecchi
Many cancer patients are at risk of developing cognitive symptoms that often become evident during or after cancer-directed therapy and may involve difficulties with attention, concentration, multitasking, executive function, and memory. Despite recent advances in identifying potential molecular and cellular mechanisms underlying cancer and chemotherapy-related cognitive impairment, there is generally a lack of effective treatment strategies, and the development of novel therapeutic interventions represents a major unmet medical need in clinical practice...
April 24, 2024: Cancer Research
#9
JOURNAL ARTICLE
Min Fu, Qian Gao, Mian Xiao, Rui-Feng Li, Xin-Yi Sun, Sheng-Lin Li, Xin Peng, Xi-Yuan Ge
Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. Here, we identified a circRNA derived from MYBL1 pre-mRNA that accompanied overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased lung metastasis and poor overall survival in ACC patients. Ectopic circMYBL1 overexpression promoted malignant phenotypes and lung metastasis of ACC cells...
April 24, 2024: Cancer Research
#10
JOURNAL ARTICLE
Yuta Ito, Amira Marouf, Yasunori Kogure, Junji Koya, Raphaël Liévin, Julie Bruneau, Mariko Tabata, Yuki Saito, Sumito Shingaki, Mitsuhiro Yuasa, Kentaro Yamaguchi, Koichi Murakami, Robert Weil, Manon Vavasseur, Guillaume P Andrieu, Mehdi Latiri, Layla Veleanu, Michaël Dussiot, Isabelle André, Akshay Joshi, Chantal Lagresle-Peyrou, Aude Magerus, Sammara Chaubard, David Lavergne, Emmanuel Bachy, Erika Brunet, Virginie Fataccioli, Chantal Brouzes, Camille Laurent, Laurence De Leval, Alexandra Traverse-Glehen, Céline Bossard, Marie-Cécile Parrens, Véronique Meignin, Laure Philippe, Julien Rossignol, Felipe Suarez, Jean-Marie Michot, Olivier Tournilhac, Gandhi Damaj, François Lemonnier, Christine Bôle-Feysot, Patrick Nitschké, Bruno Tesson, Cécile Laurent, Thierry Molina, Vahid Asnafi, Yosaku Watatani, Kenichi Chiba, Ai Okada, Yuichi Shiraishi, Sachiko Tsukita, Koji Izutsu, Hiroaki Miyoshi, Koichi Ohshima, Seiji Sakata, Akito Dobashi, Kengo Takeuchi, Masashi Sanada, Philippe Gaulard, Arnaud Jaccard, Seishi Ogawa, Olivier Hermine, Keisuke Kataoka, Lucile Couronné
Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. Here, we performed comprehensive genetic analysis of 177 ENKTCL cases to delineate the landscape of mutations, copy number alterations (CNAs), and structural variations, identifying 34 driver genes including six previously unappreciated ones, namely HLA-B, HLA-C, ROBO1, CD58, POT1, and MAP2K1...
April 24, 2024: Cancer Research
#11
JOURNAL ARTICLE
Dazhi Wang, Iqbal Mahmud, Vijay S Thakur, Sze Kiat Tan, Daniel G Isom, David B Lombard, Mark L Gonzalgo, Oleksandr N Kryvenko, Philip L Lorenzi, Vanina T Tcheuyap, James Brugarolas, Scott M Welford
Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, is largely incurable in the metastatic setting. ccRCC is characterized by excessive lipid accumulation that protects cells from stress and promotes tumor growth, suggesting that the underlying regulators of lipid storage could represent potential therapeutic targets. Here, we evaluated the regulatory roles of GPR1 and CMKLR1, two G-protein coupled receptors of the pro-tumorigenic adipokine chemerin that is involved in ccRCC lipid metabolism...
April 19, 2024: Cancer Research
#12
JOURNAL ARTICLE
Xiyue Xu, Yidan Zhang, Yaxiao Lu, Xiaoyan Zhang, Cuicui Zhao, Jiesong Wang, Qingpei Guan, Yingfang Feng, Meng Gao, Jingwei Yu, Zheng Song, Xia Liu, Zahra Golchehre, Lanfang Li, Weicheng Ren, Qiang Pan-Hammarström, Huilai Zhang, Xianhuo Wang
Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single-cell RNA-sequencing in patients with newly diagnosed DLBCL...
April 18, 2024: Cancer Research
#13
JOURNAL ARTICLE
Ning Zhao, Yinghao Cao, Ruikang Tao, Xiuxian Zhu, Runze Li, Yajun Chen, Kaixiong Tao, Lei Li, Hengyu Chen, Xianxiong Ma
Circular RNAs (circRNAs) are a class of covalently closed single-stranded loop RNAs that have been implicated to play a functional role in almost all types of cancers. Previous studies have revealed that circMYBL2 acts as a tumor-promoting circRNA. Here, we found that circMYBL2 in colorectal cancer (CRC) encodes a 185-amino acid protein, p185. Functionally, circMYBL2-encoded p185 suppressed the growth and aggressiveness of CRC cells in vitro and in vivo. Mechanistically, p185 counteracted UCHL3-mediated deubiquitination of phosphoglycerate dehydrogenase (PHGDH) by competitively binding to the C1 domain of UCHL3, resulting in PHGDH degradation and a subsequent reduction in serine and glycine biosynthesis...
April 18, 2024: Cancer Research
#14
JOURNAL ARTICLE
Yuto Naoi, Takao Morinaga, Joji Nagasaki, Ryo Ariyasu, Youki Ueda, Kazuo Yamashita, Wenhao Zhou, Shusuke Kawashima, Katsushige Kawase, Akiko Honobe-Tabuchi, Takehiro Ohnuma, Tatsuyoshi Kawamura, Yoshiyasu Umeda, Yu Kawahara, Yasuhiro Nakamura, Yukiko Kiniwa, Osamu Yamasaki, Satoshi Fukushima, Masahito Kawazu, Yutaka Suzuki, Hiroyoshi Nishikawa, Toyoyuki Hanazawa, Mizuo Ando, Takashi Inozume, Yosuke Togashi
T cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T cell exhaustion, such as PD-1, can reinvigorate tumor-specific T cells and activate anti-tumor immunity in various types of cancer. Here, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA-sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to cancer immunotherapy. CD106 in tumor-specific T cells suppressed anti-tumor immunity both in vitro and in vivo, and loss of CD106 in CD8+ T cells suppressed tumor growth and improved response to PD-1 blockade...
April 18, 2024: Cancer Research
#15
JOURNAL ARTICLE
Fc-silent anti-TIGIT antibodies potentiate anti-tumor immunity without depleting regulatory T cells.
Dana Piovesan, Amber E de Groot, Soonweng Cho, Amy E Anderson, Rebecca D Ray, Amita Patnaik, Paul G Foster, Casey G Mitchell, Alejandra Y Lopez Espinoza, Wandi S Zhu, Carlo E Stagnaro, Hema Singh, Xiaoning Zhao, Lisa Seitz, Nigel P Walker, Matthew J Walters, Kelsey E Sivick
TIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand whether there is therapeutic benefit from Fcγ receptor (FcγR) binding...
April 18, 2024: Cancer Research
#16
JOURNAL ARTICLE
Jennifer A Waters, Mikella Robinson, Omar Lujano-Olazaba, Cassidy Lucht, Samuel F Gilbert, Carrie D House
Ovarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. Improved understanding of the tumor supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis. Here, we showed that omental preadipocytes enhance the tumor initiation capacity of ovarian cancer cells. Secreted factors from preadipocytes supported cancer cell viability during nutrient and isolation stress and enabled prolonged proliferation...
April 18, 2024: Cancer Research
#17
JOURNAL ARTICLE
Moriah Cunningham, Matthew J Schiewer
PARP is a nuclear enzyme with a major function in the DNA damage response. PARP inhibitors (PARPi) have been developed for treating tumors harboring homologous recombination repair (HRR) defects that lead to a dependency on PARP. There are currently three PARPi approved for use in advanced prostate cancer (PCa), and several others are in clinical trials for this disease. Recent clinical trial results have reported differential efficacy based on the specific PARPi utilized as well as patient race. There is a racial disparity in PCa, where African American (AA) males are twice as likely to develop and die from the disease compared to European American (EA) males...
April 18, 2024: Cancer Research
#18
JOURNAL ARTICLE
Jacob Chen Ming Low, Jianbo Cao, Friederike Hesse, Alan J Wright, Anastasia Tsyben, Islam Alshamleh, Richard Mair, Kevin M Brindle
Metabolic subtypes of glioblastoma have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. Here, we used 2H magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) measurements of [6,6'-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived glioblastoma xenografts in vivo. The metabolism of patient-derived cells was first characterized in vitro by measuring the oxygen consumption rate, a marker of mitochondrial TCA cycle activity, as well as the extracellular acidification rate and 2H-labeled lactate production from [6,6'-2H2]glucose, which are markers of glycolytic activity...
April 18, 2024: Cancer Research
#19
JOURNAL ARTICLE
Jesse Boumelha, Andrea de Castro, Nourdine Bah, Hongui Cha, Sophie de Carné Trécesson, Sareena Rana, Mona Tomaschko, Panayiotis Anastasiou, Edurne Mugarza, Christopher Moore, Robert Goldstone, Philip East, Kevin Litchfield, Se-Hoon Lee, Miriam Molina-Arcas, Julian Downward
Oncogenic KRAS impairs anti-tumor immune responses. As effective strategies to combine KRAS inhibitors and immunotherapies have so far proven elusive, a better understanding of how oncogenic KRAS drives immune evasion is needed to identify approaches that could sensitize KRAS-mutant lung cancer to immunotherapy. In vivo CRISPR-Cas9 screening in an immunogenic murine lung cancer model identified mechanisms by which oncogenic KRAS promotes immune evasion, most notably via upregulation of immunosuppressive cyclooxygenase-2 (COX-2) in cancer cells...
April 18, 2024: Cancer Research
#20
JOURNAL ARTICLE
Seung-Jin Park, Shinyeong Ju, Sung-Ho Goh, Byoung-Ha Yoon, Jong-Lyul Park, Jeong-Hwan Kim, Seonjeong Lee, Sang-Jin Lee, Yumi Kwon, Wonyeop Lee, Kyung Chan Park, Geon Kook Lee, Seog Yun Park, Sunshin Kim, Seon-Young Kim, Ji-Youn Han, Cheolju Lee
UNLABELLED: Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, particularly in women. EGFR mutations and anaplastic lymphoma kinase (ALK) fusions are major genetic alterations observed in NSLA, and NSLA with these alterations have been well studied and can be treated with targeted therapies. To provide insights into the molecular profile of NSLA without EGFR and ALK alterations (NENA), we selected 141 NSLA tissues and performed proteogenomic characterization, including whole genome sequencing (WGS), transcriptomic, methylation EPIC array, total proteomic, and phosphoproteomic analyses...
April 12, 2024: Cancer Research
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