journal
https://read.qxmd.com/read/38016110/one-mutation-to-rule-them-all-mutant-kras-controls-tumor-intrinsic-and-microenvironment-signaling
#1
JOURNAL ARTICLE
Sören Müller, Akshay T Krishnamurty
In a recent study published in Cancer Discovery, Hsu and colleagues employ an elegant combination of single-cell and bulk RNA-seq experiments from mouse and human colorectal cancer (CRC) samples, patient-derived organoids, 2D in vitro systems, and in vivo validation in genetically engineered CRC mouse models to investigate how mutant KRAS (KRAS*) impacts the tumor microenvironment. They identify a molecular signaling cascade downstream of KRAS* that activates a specific program of lipid-rich CAFs, promoting tumor angiogenesis and progression...
November 28, 2023: Cancer Research
https://read.qxmd.com/read/38016109/a-multi-ethnic-germline-somatic-association-database-deciphers-multilayered-and-interconnected-genetic-mutations-in-cancer
#2
JOURNAL ARTICLE
Junyi Xin, Zongchao Mo, Rui-Chao Chai, Wei Hua, Jiguang Wang
Inherited germline and acquired somatic alterations can both promote human tumor development. Elucidating the cooperation between somatic and germline genetic alterations that drive tumorigenesis could help inform precision cancer prevention and treatment strategies. Here, leveraging genomic genotyping and sequencing data from 9,029 cancer patients with European, East Asian, and African ancestry, we performed a pan-cancer analysis to evaluate the associations between germline single nucleotide polymorphisms (SNPs) and somatic alterations, including single-nucleotide variant and small insertion/deletion mutations, copy number variation (CNV), tumor mutational burden (TMB), and mutational signatures...
November 28, 2023: Cancer Research
https://read.qxmd.com/read/37991737/sumoylation-driven-mrna-circularization-enhances-translation-and-promotes-lymphatic-metastasis-of-bladder-cancer
#3
JOURNAL ARTICLE
Yue Zhao, Jiancheng Chen, Hanhao Zheng, Yuming Luo, Mingjie An, Yan Lin, Mingrui Pang, Yuanlong Li, Yao Kong, Wang He, Tianxin Lin, Changhao Chen
Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer (BCa) and correlated with poor prognosis of patients. DHCR24 promoted lymphangiogenesis and LN metastasis of BCa in vitro and in vivo. Mechanistically, DHCR24 mediated and recognized the SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization and eIF4F initiation complex assembly by enhancing hnRNPA2B1-eIF4G1 interaction...
November 22, 2023: Cancer Research
https://read.qxmd.com/read/37991725/prmt1-inhibition-activates-the-interferon-pathway-to-potentiate-antitumor-immunity-and-enhance-checkpoint-blockade-efficacy-in-melanoma
#4
JOURNAL ARTICLE
Hongru Tao, Chen Jin, Liyuan Zhou, Zhenzhong Deng, Xiao Li, Wenzhen Dang, Shijie Fan, Bing Li, Fei Ye, JunYan Lu, Xiangqian Kong, Chuanpeng Liu, Cheng Luo, Yuanyuan Zhang
Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyl transferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8+ T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8+T cells in vivo...
November 22, 2023: Cancer Research
https://read.qxmd.com/read/37987734/topoisomerase-1-inhibition-in-myc-driven-cancer-promotes-aberrant-r-loop-accumulation-to-induce-synthetic-lethality
#5
JOURNAL ARTICLE
Peter Lin, Corey Lourenco, Jennifer Cruickshank, Luis Palomero, Jenna E van Leeuwen, Amy H Y Tong, Katherine Chan, Samah El Ghamrasni, Miquel Angel Pujana, David W Cescon, Jason Moffat, Linda Z Penn
UNLABELLED: MYC is a central regulator of gene transcription and is frequently dysregulated in human cancers. As targeting MYC directly is challenging, an alternative strategy is to identify specific proteins or processes required for MYC to function as a potent cancer driver that can be targeted to result in synthetic lethality. To identify potential targets in MYC-driven cancers, we performed a genome-wide CRISPR knockout screen using an isogenic pair of breast cancer cell lines in which MYC dysregulation is the switch from benign to transformed tumor growth...
November 21, 2023: Cancer Research
https://read.qxmd.com/read/37967363/r-loop-accumulation-in-spliceosome-mutant-leukemias-confers-sensitivity-to-parp1-inhibition-by-triggering-transcription-replication-conflicts
#6
JOURNAL ARTICLE
Zhiyan Silvia Liu, Sayantani Sinha, Maxwell Bannister, Axia Song, Erica Arriaga-Gomez, Alexander J McKeeken, Elizabeth A Bonner, Benjamin K Hanson, Martina Sarchi, Kouhei Takashima, Dawei Zong, Victor M Corral, Evan Nguyen, Jennifer Yoo, Wannasiri Chiraphapphaiboon, Cassandra Leibson, Matthew C McMahon, Sumit Rai, Elizabeth M Swisher, Zohar Sachs, Srinivas Chatla, Derek L Stirewalt, H Joachim Deeg, Tomasz Skorski, Eirini P Papapetrou, Matthew J Walter, Timothy A Graubert, Sergei Doulatov, Stanley C Lee, Hai Dang Nguyen
RNA splicing factor (SF) gene mutations are commonly observed in patients with myeloid malignancies. Here we showed that SRSF2- and U2AF1-mutant leukemias are preferentially sensitive to PARP inhibitors (PARPi) despite being proficient in homologous recombination repair. Instead, SF-mutant leukemias exhibited R-loop accumulation that elicited an R-loop associated PARP1 response, rendering cells dependent on PARP1 activity for survival. Consequently, PARPi induced DNA damage and cell death in SF-mutant leukemias in an R-loop dependent manner...
November 15, 2023: Cancer Research
https://read.qxmd.com/read/37963212/deep-learning-enables-spatial-mapping-of-the-mosaic-microenvironment-of-myeloma-bone-marrow-trephine-biopsies
#7
JOURNAL ARTICLE
Yeman B Hagos, Catherine S Y Lecat, Dominic Patel, Anna Mikolajczak, Simon P Castillo, Emma J Lyon, Kane Foster, Thien-An Tran, Lydia S H Lee, Manuel Rodriguez-Justo, Kwee L Yong, Yinyin Yuan
Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphological, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse cellular communities and mosaic tissue habitats, we developed a superpixel-inspired deep learning method (MoSaicNet) that adapts to complex tissue architectures and a cell imbalance aware deep learning pipeline (AwareNet) to enable accurate detection and classification of rare cell types in multiplex immunohistochemistry images...
November 14, 2023: Cancer Research
https://read.qxmd.com/read/37963210/the-chromatin-remodeler-chd4-sustains-ewing-sarcoma-cell-survival-by-controlling-global-chromatin-architecture
#8
JOURNAL ARTICLE
Joana G Marques, Blaz Pavlovic, Quy A Ngo, Gloria Pedot, Michaela Roemmele, Larissa Volken, Samanta Kisele, Romain Perbet, Marco Wachtel, Beat W Schafer
Ewing sarcoma is an aggressive cancer with a defective response to DNA damage leading to an enhanced sensitivity to genotoxic agents. Mechanistically, Ewing sarcoma is driven by the fusion transcription factor EWS-FLI1 which reprograms the tumor cell epigenome. The NuRD complex is an important regulator of chromatin function, controlling both gene expression and DNA damage repair, and has been associated with EWS-FLI1 activity. Here, a NuRD-focused CRISPR/Cas9 inactivation screen identified the helicase CHD4 as essential for Ewing sarcoma cell proliferation...
November 14, 2023: Cancer Research
https://read.qxmd.com/read/37963209/lineage-plasticity-the-new-cancer-hallmark-on-the-block
#9
JOURNAL ARTICLE
Arnav Mehta, Ben Z Stanger
Plasticity refers to the ability of cells to adopt a spectrum of states or phenotypes. In cancer, it is a critical contributor to tumor initiation, progression, invasiveness, and therapy resistance, and it has recently been recognized as an emerging cancer hallmark. Plasticity can occur as a result of cell-intrinsic factors (e.g. genetic, transcriptional or epigenetic fluctuations), or through cell-extrinsic cues (e.g. signaling from components of the tumor microenvironment (TME) or selective pressure from therapy)...
November 14, 2023: Cancer Research
https://read.qxmd.com/read/37963207/neuronal-activity-promotes-glioma-progression-by-inducing-proneural-to-mesenchymal-transition-in-glioma-stem-cells
#10
JOURNAL ARTICLE
Xiaofan Guo, Wei Qiu, Chaochao Wang, Yanhua Qi, Boyan Li, Shaobo Wang, Rongrong Zhao, Bo Cheng, Xiao Han, Hao Du, Zijie Gao, Ziwen Pan, Shulin Zhao, Gang Li, Hao Xue
Neuronal activity can drive progression of high-grade glioma by mediating mitogen production and neuron-glioma synaptic communications. Glioma stem cells (GSCs) also play a significant role in progression, therapy resistance, and recurrence in glioma, which implicates potential crosstalk between neuronal activity and GSC biology. Here, we manipulated neuronal activity using chemogenetics in vitro and in vivo to study how it influences GSCs. Neuronal activity supported glioblastoma progression and radioresistance through exosome-induced proneural-to-mesenchymal transition (PMT) of GSCs...
November 14, 2023: Cancer Research
https://read.qxmd.com/read/37963200/circmmp2-6-7-cooperates-with-%C3%AE-catenin-and-prmt5-to-disrupt-bone-homeostasis-and-promote-breast-cancer-bone-metastasis
#11
JOURNAL ARTICLE
Yingru Xu, Xincheng Li, Shuxia Zhang, Miaoling Tang, Ruyuan Yu, Xinyi Liao, Ziwen Li, Man Li, Suwen Chen, Wanying Qian, Libing Song, ZunFu Ke, Jun Li
The bone is the most common site of distant metastasis of breast cancer, which leads to serious skeletal complications and mortality. Understanding the mechanisms underlying breast cancer bone metastasis would provide potential strategies for the prevention and treatment of breast cancer bone metastasis. In the current study, we identified a circular RNA that we named circMMP2(6,7) that was significantly upregulated in bone metastatic breast cancer tissues and correlated with breast cancer-bone metastasis. Upregulation of circMMP2(6,7) dramatically enhanced the metastatic capability of breast cancer cells to the bone via inducing bone metastatic niche formation by disrupting bone homeostasis...
November 14, 2023: Cancer Research
https://read.qxmd.com/read/37963197/rna-methyltransferase-ftsj3-regulates-the-type-i-interferon-pathway-to-promote-hepatocellular-carcinoma-immune-evasion
#12
JOURNAL ARTICLE
Qiuyu Zhuang, Zhiguo Dai, Xuechun Xu, Shaoyi Bai, Yindan Zhang, Youshi Zheng, Xiaohua Xing, En Hu, Yingchao Wang, Wuhua Guo, Bixing Zhao, Yongyi Zeng, Xiaolong Liu
Immunotherapies such as immune checkpoint blockade have achieved remarkable success in treating cancer. Unfortunately, response rates have been limited in multiple cancers including hepatocellular carcinoma (HCC). The critical function of epigenetics in tumor immune evasion and anti-tumor immunity supports harnessing epigenetic regulators as a potential strategy to enhance the efficacy of immunotherapy. Here, we discovered a tumor-promoting function of FTSJ3, an RNA 2'-O-methyltransferase, in HCC by suppressing anti-tumor immune responses...
November 14, 2023: Cancer Research
https://read.qxmd.com/read/37963187/small-cell-lung-cancer-plasticity-enables-nfib-independent-metastasis
#13
JOURNAL ARTICLE
Julie H Ko, Kyle E Lambert, Debadrita Bhattacharya, Myung Chang Lee, Caterina I Colon, Haley Hauser, Julien Sage
Metastasis is a major cause of morbidity and mortality in patients with cancer, highlighting the need to identify improved treatment and prevention strategies. Previous observations in pre-clinical models and tumors from patients with small cell lung cancer (SCLC), a fatal form of lung cancer with high metastatic potential, identified the transcription factor NFIB as a driver of tumor growth and metastasis. However, investigation into the requirement for NFIB activity for tumor growth and metastasis in relevant in vivo models is needed to establish NFIB as a therapeutic target...
November 14, 2023: Cancer Research
https://read.qxmd.com/read/37934116/glucose-deprivation-promotes-pseudo-hypoxia-and-de-differentiation-in-lung-adenocarcinoma
#14
JOURNAL ARTICLE
Pasquale Saggese, Aparamita Pandey, Martín Alcaraz, Eileen Fung, Abbie Hall, Jane Yanagawa, Erika F Rodriguez, Tristan R Grogan, Giorgio Giurato, Giovanni Nassa, Annamaria Salvati, Orian S Shirihai, Alessandro Weisz, Steven M Dubinett, Claudio Scafoglio
Increased utilization of glucose is a hallmark of cancer. Sodium-glucose transporter 2 (SGLT2) is a critical player in glucose uptake in early-stage and well-differentiated lung adenocarcinoma (LUAD). SGLT2 inhibitors, which are FDA-approved for diabetes, heart failure, and kidney disease, have been shown to significantly delay LUAD development and prolong survival in murine models and in retrospective studies in diabetic patients, suggesting that they may be re-purposed for lung cancer. Despite the anti-tumor effects of SGLT2 inhibition, tumors eventually escape treatment...
November 7, 2023: Cancer Research
https://read.qxmd.com/read/37934115/crispr-screening-identifies-mechanisms-of-resistance-to-krasg12c-and-shp2-inhibitor-combinations-in-non-small-cell-lung-cancer
#15
JOURNAL ARTICLE
Anirudh Prahallad, Andreas Weiss, Hans Voshol, Grainne Kerr, Kathleen Sprouffske, Tina Yuan, David Ruddy, Morgane Meistertzheim, Malika Kazic-Legueux, Tina Kottarathil, Michelle Piquet, Yichen Cao, Laetitia Martinuzzi-Duboc, Alexandra Buhles, Flavia Alder, Salvatore Mannino, Luca Tordella, Laurent Sansregret, Sauveur-Michel Maira, Diana Graus Porta, Carmine Fedele, Saskia M Brachmann
Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated non-small cell lung cancer (NSCLC) and other solid tumor malignancies, response is limited by multiple mechanisms of resistance. The KRASG12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 ± TNO155, alone or combined with the PI3Kα inhibitor alpelisib and/or the CDK4/6 inhibitor ribociclib, in xenograft models derived from a KRASG12C-mutant NSCLC line and investigated the genetic mechanisms associated with loss of response to combined KRASG12C/SHP2 inhibition...
November 7, 2023: Cancer Research
https://read.qxmd.com/read/37934103/tead-inhibition-overcomes-yap1-taz-driven-primary-and-acquired-resistance-to-krasg12c-inhibitors
#16
JOURNAL ARTICLE
A Cole Edwards, Clint A Stalnecker, Alexis Jean Morales, Khalilah E Taylor, Jennifer E Klomp, Jeffrey A Klomp, Andrew M Waters, Niranjan Sudhakar, Jill Hallin, Tracy T Tang, Peter Olson, Leonard Post, James G Christensen, Adrienne D Cox, Channing J Der
Primary/intrinsic and treatment-induced acquired resistance limit the initial response rate to and long-term efficacy of direct inhibitors of the KRASG12C mutant in cancer. To identify potential mechanisms of resistance, we applied a CRISPR/Cas9 loss-of-function screen and observed loss of multiple components of the Hippo tumor suppressor pathway, which acts to suppress YAP1/TAZ-regulated gene transcription. YAP1/TAZ activation impaired the anti-proliferative and pro-apoptotic effects of KRASG12C inhibitor (G12Ci) treatment in KRASG12C-mutant cancer cell lines...
November 7, 2023: Cancer Research
https://read.qxmd.com/read/37930937/spatial-and-single-cell-transcriptomics-reveal-a-cancer-associated-fibroblast-subset-in-hnscc-that-restricts-infiltration-and-anti-tumor-activity-of-cd8-t-cells
#17
JOURNAL ARTICLE
Chuwen Li, Haiyan Guo, Peisong Zhai, Ming Yan, Chun Liu, Xiaoning Wang, Chaoji Shi, Jiang Li, Tong Tong, Zhiyuan Zhang, Hailong Ma, Jianjun Zhang
Although immunotherapy can prolong survival in some patients with head and neck squamous cell carcinoma (HNSCC), the response rate remains low. Clarification of the critical mechanisms regulating CD8+ T-cell infiltration and dysfunction in the tumor microenvironment could help maximize the benefit of immunotherapy for treating HNSCC. Here, we performed spatial transcriptomic analysis of HNSCC specimens with differing immune infiltration and single-cell RNA sequencing of five pairs of tumor and adjacent tissues, revealing specific CAF subsets related to CD8+ T-cell infiltration restriction and dysfunction...
November 6, 2023: Cancer Research
https://read.qxmd.com/read/37922465/targeting-mthfd2-to-exploit-cancer-specific-metabolism-and-the-dna-damage-response
#18
JOURNAL ARTICLE
Louise Ramos, Martin Henriksson, Thomas Helleday, Alanna C Green
The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across numerous cancer types, promotes growth and metastasis of cancer, and correlates with poorer survival. Recent studies have developed small molecule inhibitors of the isozymes MTHFD2 and MTHFD1 that show promise as anti-cancer agents through different mechanisms. This review discusses the current understanding of the function of MTHFD2 in cancer and the status of inhibitors for treating MTHFD2-overexpressing cancers...
November 3, 2023: Cancer Research
https://read.qxmd.com/read/37921711/erythroid-differentiation-enhances-rna-mis-splicing-in-sf3b1-mutant-myelodysplastic-syndromes-with-ring-sideroblasts
#19
JOURNAL ARTICLE
Pedro L Moura, Teresa Mortera Blanco, Isabel J Hofman, Gabriele Todisco, Warren W Kretzschmar, Ann-Charlotte Björklund, Maria Creignou, Michael Hagemann-Jensen, Christoph Ziegenhain, David Cabrerizo Granados, Indira Barbosa, Gunilla Walldin, Monika Jansson, Neil Ashley, Adam J Mead, Vanessa Lundin, Marios Dimitriou, Tetsuichi Yoshizato, Petter S Woll, Seishi Ogawa, Rickard Sandberg, Sten-Eirik W Jacobsen, Eva Hellström-Lindberg
Myelodysplastic syndromes with ring sideroblasts (MDS-RS) commonly develop from hematopoietic stem cells (HSC) bearing mutations in the splicing factor SF3B1 (SF3B1mt). Direct studies into MDS-RS pathobiology have been limited by a lack of model systems that fully recapitulate erythroid biology and RS development and the inability to isolate viable human RS. Here, we combined successful direct RS isolation from patient samples, high-throughput multiomics analysis of cells encompassing the SF3B1mt stem-erythroid continuum, and functional assays to investigate the impact of SF3B1mt on erythropoiesis and RS accumulation...
November 3, 2023: Cancer Research
https://read.qxmd.com/read/37906431/metabolomic-rewiring-promotes-endocrine-therapy-resistance-in-breast-cancer
#20
JOURNAL ARTICLE
Songyeon Ahn, Jun Hyoung Park, Sandra L Grimm, Danthasinghe Waduge Badrajee Piyarathna, Tagari Samanta, Vasanta Putluri, Dereck Mezquita, Suzanne A W Fuqua, Nagireddy Putluri, Cristian Coarfa, Benny Abraham Kaipparettu
Approximately one-third of endocrine-treated women with estrogen receptor-alpha positive (ER+) breast cancers (BC) are at risk of recurrence due to intrinsic or acquired resistance. Thus, it is vital to understand the mechanisms underlying endocrine therapy resistance in ER+ BC to improve patient treatment. Mitochondrial fatty acid β-oxidation (FAO) has been shown to be a major metabolic pathway in triple-negative BC (TNBC) that can activate Src signaling. Here, we found metabolic reprogramming that increases FAO in ER+ BC as a mechanism of resistance to endocrine therapy...
October 31, 2023: Cancer Research
journal
journal
20068
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.