Article
Oncology
Michael P. Kim, Xinqun Li, Jenying Deng, Yun Zhang, Bingbing Dai, Kendra L. Allton, Tara G. Hughes, Christian Siangco, Jithesh J. Augustine, Ya'an Kang, Joy M. McDaniel, Shunbin Xiong, Eugene J. Koay, Florencia McAllister, Christopher A. Bristow, Timothy P. Heffernan, Anirban Maitra, Bin Liu, Michelle C. Barton, Amanda R. Wasylishen, Jason B. Fleming, Guillermina Lozano
Summary: The study found that oncogenic KRAS effectors activate CREB1 to interact with mutant p53, promoting PDAC metastasis. Inhibiting CREB1 can reduce the expression of FOXA1 and beta-catenin, slowing down PDAC metastasis.
Article
Biology
Wen-Cheng Chung, Lavanya Challagundla, Yunyun Zhou, Min Li, Azeddine Atfi, Keli Xu
Summary: Notch signaling in the pancreas has dual roles in cancer, acting both as an oncogene and a tumor suppressor. Deletion of Jag1 in combination with oncogenic Kras(G12D) leads to development of cystic neoplasms rather than ductal adenocarcinoma in mice, with Jag1 acting as a tumor suppressor by delaying precursor lesions. Loss of Jag1 promotes a phenotypic switch from malignant carcinoma to benign cystic lesions. JAG1 expression in pancreatic cancer patients is higher in cancerous tissue, associated with poor overall survival, and correlated with SOX9 expression which also has similar associations with survival outcomes.
LIFE SCIENCE ALLIANCE
(2021)
Review
Oncology
Sapana Bansod, Paarth B. Dodhiawala, Kian-Huat Lim
Summary: The oncogenic KRAS signaling drives effector cascades contributing to pancreatic cancer cells' malignant behavior and the fibro-inflammatory microenvironment. However, targeting KRAS or its direct effector cascades has been clinically ineffective, possibly due to the complex onco-inflammatory network between tumor cells and the non-neoplastic cells in the microenvironment. This review discusses the need to understand the bidirectional signaling interplay in order to develop novel therapeutic opportunities for pancreatic ductal adenocarcinoma.
Article
Biochemistry & Molecular Biology
Junhui Sun, Qi Chen, Jianlong Ma
Summary: Researchers used a zebrafish liver cancer model to study hepatocyte dedifferentiation in hepatocellular carcinoma and found that Notch signaling pathway was upregulated during this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Pingping Hou, Xingdi Ma, Zecheng Yang, Qiang Zhang, Chang-Jiun Wu, Jun Li, Lin Tan, Wantong Yao, Liang Yan, Xin Zhou, Alec C. Kimmelman, Philip L. Lorenzi, Jianhua Zhang, Shan Jiang, Denise Spring, Y. Alan Wang, Ronald A. DePinho
Summary: The study uncovers USP21 as a driver of KRAS*-independent PDAC growth by inducing macropinocytosis, which maintains intracellular amino acid levels. USP21 may play a role in affecting responsiveness to emergent anti-KRAS* therapy.
GENES & DEVELOPMENT
(2021)
Review
Medicine, General & Internal
Xuqing Shen, Ningning Niu, Jing Xue
Summary: KRAS activation is a key driver of PDAC initiation and progression, and PDAC cells undergo extensive metabolic reprogramming to meet their extreme energy and biomass demands.
JOURNAL OF TRANSLATIONAL INTERNAL MEDICINE
(2022)
Article
Hematology
Yajie Shen, Jingqi Zhou, Kui Nie, Shuhua Cheng, Zhengming Chen, Wenhan Wang, Weiqing Wei, Daiji Jiang, Zijing Peng, Yizhuo Ren, Yirong Zhang, Qiuju Fan, Kristy L. Richards, Yitao Qi, Jinke Cheng, Wayne Tam, Jiao Ma
Summary: This study reveals that SOX9 overexpression, particularly in DLBCLs with IGH-BCL2 translocations, is associated with an advanced stage of disease. Silencing of SOX9 decreases cell proliferation and induces G1/S arrest and apoptosis in DLBCL cells, both in vitro and in vivo. The study identifies DHCR24 as a direct target of SOX9 and demonstrates that the SOX9-DHCR24-cholesterol biosynthesis axis plays a role in lymphomagenesis. The findings suggest that this axis could serve as a novel treatment target for DLBCLs.
Review
Oncology
Yongde Luo, Xiaokun Li, Jianjia Ma, James L. Abbruzzese, Weiqin Lu
Summary: Mutant KRAS is a key driver of pancreatic cancer, but its activity is regulated by upstream stimuli. Obesity exacerbates mutant KRAS-mediated pathologies, but the mechanistic link between obesity and pancreatic cancer remains unclear.
Article
Cell Biology
Krishnan K. Mahadevan, Valerie S. Lebleu, Elena Ramirez, Yang Chen, Bingrui Li, Amari M. Sockwell, Mihai Gagea, Hikaru Sugimoto, Lakshmi Kavitha Sthanam, Desiree Tampe, Michael Zeisberg, Haoqiang Ying, Abhinav K. Jain, Ronald A. Depinho, Anirban Maitra, Kathleen M. Mcandrews, Raghu Kalluri
Summary: Oncogenic KRASG12D is critical for PDAC and represses tumor immunity. Elimination of KRAS* leads to reactivation of FAS and CD8+ T cell-mediated apoptosis, promoting tumor eradication. High KRAS expression in PDAC tumors is associated with lower proportion of CD8+ T cells and shorter survival. Combination of KRAS* targeting with immunotherapy can control PDAC effectively.
DEVELOPMENTAL CELL
(2023)
Article
Cell & Tissue Engineering
Shuang Chen, Kang Li, Xinqi Zhong, Ganping Wang, Xiaocheng Wang, Maosheng Cheng, Jie Chen, Zhi Chen, Jianwen Chen, Caihua Zhang, Gan Xiong, Xiuyun Xu, Demeng Chen, Heping Li, Liang Peng
Summary: Our study demonstrates that Sox9-expressing cells promote lung tissue regeneration, with their ablation leading to severe radiation damage phenotypes. Through analysis of an online scRNA-Seq dataset, we found that the PI3K/AKT pathway is enriched in Sox9-expressing cells during lung epithelium regeneration.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Sultan Alhayyani, Louise McLeod, Alison C. West, Jesse J. Balic, Christopher Hodges, Liang Yu, Julian A. Smith, Zdenka Prodanovic, Steven Bozinovski, Beena Kumar, Saleela M. Ruwanpura, Mohamed I. Saad, Brendan J. Jenkins
Summary: The oncogenic potential of the STAT3 transcription factor in many human cancers, including lung cancer, is largely attributed to its nuclear activity as a tyrosine-phosphorylated transcription factor. However, an alternate pool of serine-phosphorylated STAT3 in mitochondria has been shown to promote tumorigenesis in a limited number of mutant RAS-addicted neoplasms. In mutant KRAS-driven lung adenocarcinoma, the transcriptional activity of pS(727)-STAT3 is essential for promoting a hyper-proliferative state in cancer cells through metabolic reprogramming.
Article
Multidisciplinary Sciences
Derek K. Cheng, Tobiloba E. Oni, Jennifer S. Thalappillil, Youngkyu Park, Hsiu-Chi Ting, Brinda Alagesan, Nadia V. Prasad, Kenneth Addison, Keith D. Rivera, Darryl J. Pappin, Linda Van Aelst, David A. Tuveson
Summary: The study identified protein interactors of active KRAS in PDAC cells using proximity labeling, revealing that RSK1 selectively interacts with membrane-bound KRASG12D through NF1 and SPRED2. It was found that membrane RSK1 mediates negative feedback on WT RAS signaling and impedes the proliferation of pancreatic cancer cells upon the ablation of mutant KRAS in PDAC, highlighting the role of WT RAS signaling in promoting adaptive resistance to mutant KRAS-specific inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Mohamad Assi, Younes Achouri, Axelle Loriot, Nicolas Dauguet, Hajar Dahou, Jonathan Baldan, Maxime Libert, Jean S. Fain, Carmen Guerra, Luc Bouwens, Mariano Barbacid, Frederic P. Lemaigre, Patrick Jacquemin
Summary: The study demonstrates that pancreatic acinar cells become less sensitive to tumorigenesis induced by oncogenic Kras mutations after birth, due to low expression of KRAS and its effectors. Pancreatitis induces the expression of KRAS and its effectors, requiring the activity of EGFR. Expression of C-RAF in adult pancreas is essential for pancreatic tumorigenesis.
Article
Oncology
Justin K. Messex, Kiyah L. A. Adams, William G. Hawkins, David DeNardo, Nabeel Bardeesy, Daniel D. Billadeau, Geou-Yarh Liou
Summary: This study highlights the role of cytokine CCL15 in regulating PDAC cell migration and invasion, and demonstrates a new mechanism of oncogenic Kras(G12D) in modulating PDAC inflammation and spreading.
Article
Cell Biology
Preetish Kadur Lakshminarasimha Murthy, Rui Xi, Diana Arguijo, Jeffrey Everitt, Dewran D. Kocak, Yoshihiko Kobayashi, Aline Bozec, Silvestre Vicent, Shengli Ding, Gregory E. Crawford, David Hsu, Purushothama Rao Tata, Timothy Reddy, Xiling Shen
Summary: Oncogenic Kras induces cell proliferation and tumor development in epithelial tissues. The AP-1 factor, guided by the mSWI/SNF complex, controls gene expression necessary for tumor transformation. Cell-type-specific transcription factors can also retain the epigenetic memory of the tumor's cell of origin.
DEVELOPMENTAL CELL
(2022)
Article
Gastroenterology & Hepatology
Feng Wang, You-Sheng Huang, Hao-Xiang Wu, Zi-Xian Wang, Ying Jin, Yi-Chen Yao, Yan-Xing Chen, Qi Zhao, Shifu Chen, Ming-Ming He, Hui-Yan Luo, Miao-Zhen Qiu, De-Shen Wang, Feng-Hua Wang, Mingyan Xu, Yu-Hong Li, Rui-Hua Xu
Summary: The study investigated the genomic heterogeneity of circulating tumor DNA in patients with metastatic colorectal cancer during different treatments, revealing the impact of RAS/BRAF mutations on patients' treatment outcomes. The findings suggest that changes in plasma RAS/BRAF mutational status can significantly affect survival outcomes in these patients.
Article
Oncology
Shaohan Yin, Xiao Luo, Yadi Yang, Ying Shao, Lidi Ma, Cuiping Lin, Qiuxia Yang, Deling Wang, Yingwei Luo, Zhijun Mai, Weixiong Fan, Dechun Zheng, Jianpeng Li, Fengyan Cheng, Yuhui Zhang, Xinwei Zhong, Fangmin Shen, Guohua Shao, Jiahao Wu, Ying Sun, Huiyan Luo, Chaofeng Li, Yaozong Gao, Dinggang Shen, Rong Zhang, Chuanmiao Xie
Summary: This study developed a multi-scale cascaded convolutional network for brain metastasis detection and validated its accuracy. The results showed that using this system can improve the detection sensitivity of doctors and reduce reading time.
Article
Endocrinology & Metabolism
Yihui Chen, Michela Capello, Mayrim V. Rios Perez, Jody V. Vykoukal, David Roife, Ya'an Kang, Laura R. Prakash, Hiroyuki Katayama, Ehsan Irajizad, Alia Fleury, Sammy Ferri-Borgogno, Dodge L. Baluya, Jennifer B. Dennison, Kim-Anh Do, Oliver Fiehn, Anirban Maitra, Huamin Wang, Paul J. Chiao, Matthew H. G. Katz, Jason B. Fleming, Samir M. Hanash, Johannes F. Fahrmann
Summary: In this study, the researchers found that the high expression of intra-tumoral CES2 was significantly associated with poor overall survival in patients with PDAC. Knockdown of CES2 in PDAC cells inhibited cell growth and clonogenic capacity and attenuated tumor growth in a mouse model of PDAC. Furthermore, CES2 was found to promote metabolic changes through the activation of HNF4α. Targeting the CES2-sEH-HNF4α axis using CES2 or sEH inhibitors reduced cell viability in PDAC.
MOLECULAR METABOLISM
(2022)
Article
Multidisciplinary Sciences
Christophe Glorieux, Xiaojun Xia, Xin You, Zining Wang, Yi Han, Jing Yang, Gauthier Noppe, Christophe de Meester, Jianhua Ling, Annie Robert, Hui Zhang, Sheng-Ping Li, Huamin Wang, Paul J. Chiao, Li Zhang, Xiaobing Li, Peng Huang
Summary: This study investigated the impact of two common chemotherapy drugs, gemcitabine and cisplatin, on the therapeutic efficacy of PD-1 antibody in K-ras-driven cancers. The results showed that gemcitabine inhibits CD8+ T cell infiltration and antagonizes the therapeutic effect of PD-1 antibody, while cisplatin activates CD8+ T cells and shows synergistic activity with PD-1 antibody. Clinical data suggests that the combination of cisplatin and PD-1 antibody may be effective in advanced lung cancer patients with K-ras mutation.
JOURNAL OF ADVANCED RESEARCH
(2022)
Editorial Material
Oncology
Long Bai, Xiao-Luan Yan, Yun-Xin Lu, Qi Meng, Yu-Ming Rong, Liu-Fang Ye, Zhi-Zhong Pan, Bao-Cai Xing, De-Shen Wang
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Engineering, Chemical
Yeping Xie, Liufang Ye, Wenhua Chen, Pengju Liu, Yuansen Liu
Summary: This study demonstrates a method to convert waste cross-linked polyethylene (CLPE) cables into low-cost, high-strength, and all-weather electromagnetic interference (EMI) shielding materials. By utilizing selective heating mode of microwave and remaining cross-linked structure, a segregated structure with carbon nanotubes (CNTs) selectively enriched at the interfaces of the CLPE phases was successfully constructed, improving the electrical and EMI shielding properties of the composite material and exhibiting stable performance.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Qi Zhao, Feng Wang, Yan-Xing Chen, Shifu Chen, Yi-Chen Yao, Zhao-Lei Zeng, Teng-Jia Jiang, Ying-Nan Wang, Chen-Yi Wu, Ying Jing, You-Sheng Huang, Jing Zhang, Zi-Xian Wang, Ming-Ming He, Heng-Ying Pu, Zong-Jiong Mai, Qi-Nian Wu, Renwen Long, Xiaoni Zhang, Tanxiao Huang, Mingyan Xu, Miao-Zheng Qiu, Hui-Yan Luo, Yu-Hong Li, Dong-Shen Zhang, Wei-Hua Jia, Gong Chen, Pei-Rong Ding, Li-Ren Li, Zheng-Hai Lu, Zhi-Zhong Pan, Rui-Hua Xu
Summary: Through ultradeep whole-exome sequencing, we identified 46 significantly mutated genes associated with CRC and proposed a subtyping strategy that classifies CRC patients into four genomic subtypes with distinct clinical characteristics. Additionally, we found that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Zhen Zhang, Zi-Xian Wang, Yan-Xing Chen, Hao-Xiang Wu, Ling Yin, Qi Zhao, Hui-Yan Luo, Zhao-Lei Zeng, Miao-Zhen Qiu, Rui-Hua Xu
Summary: By analyzing single-cell RNA sequencing data from ICI-treated patients, it was found that cancer stemness may be associated with resistance to ICI treatment. The developed novel stemness signature (Stem.Sig) showed improved predictive performance for ICI response across multiple cancers, potentially serving as a competitive tool for patient selection in immunotherapy.
Article
Gastroenterology & Hepatology
Ting Li, Yue-Tao Tan, Yan-Xing Chen, Xiao-Jun Zheng, Wen Wang, Kun Liao, Hai-Yu Mo, Junzhong Lin, Wei Yang, Hai-Long Piao, Rui-Hua Xu, Huai-Qiang Ju
Summary: Methionine and YTHDF1 play a critical role in anticancer immunity through regulating the functions of T cells. Targeting methionine metabolism or YTHDF1 could be a potential new strategy for cancer immunotherapy.
Letter
Oncology
Rui Liu, Panpan Liu, Huichang Bi, Jianhua Ling, Huiqin Zhang, Mingquan Zhang, Yumin Hu, Paul J. Chiao, Peng Huang, Jinyun Liu
CANCER COMMUNICATIONS
(2023)
Article
Oncology
Xiao-Li Wei, Yang Zhang, Hong-Yun Zhao, Wen-Feng Fang, Hui-Yan Luo, Miao-Zhen Qiu, Ming-Ming He, Ben-Yan Zou, Jie Xie, Chun-Lei Jin, Xian-Feng Zhou, Feng Wang, Feng-Hua Wang, Yu-Hong Li, Zhi-Qiang Wang, Rui-Hua Xu
Summary: This report presents the results of two phase I trials evaluating the tolerability, safety, and preliminary antitumor activity of SHR7390 monotherapy and SHR7390 in combination with camrelizumab in patients with advanced solid tumors and treatment-refractory advanced or metastatic colorectal cancer (CRC).
Retraction
Cell Biology
Hong-En Yu, Feng Wang, Fang Yu, Zhao-Lei Zeng, Yun Wang, Yun-Xin Lu, Ying Jin, De-Shen Wang, Miao-Zhen Qiu, Heng-Ying Pu, Tie-Bang Kang, Dan Xie, Huai-Qiang Ju, Rui-Hua Xu, Hui-Yan Luo
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Yi Han, Yan-Yu Zhang, Yi-Qian Pan, Xiao-Jun Zheng, Kun Liao, Hai-Yu Mo, Hui Sheng, Qi-Nian Wu, Ze-Xian Liu, Zhao-Lei Zeng, Wei Yang, Shu-Qiang Yuan, Peng Huang, Huai-Qiang Ju, Rui-Hua Xu
Summary: Interleukin-10 (IL-10) plays a role in inflammation and tumor progression, but its role in cancer is unclear. This study found that IL-10 stimulation leads to acetylation of nicotin-amide nucleotide transhydrogenase (NNT) in cancer cells, which induces the translocation of p300/CBP-associated factor (PCAF) to the mitochondria. This acetylation enhances NNT activity, increases NADPH production, and protects tumor cells from ferroptosis, contributing to tumor immune evasion.
Article
Oncology
Zeyi Guo, Qingyu Xie, Yanping Wu, Haiyu Mo, Jiajun Zhang, Guolin He, Zhongzhe Li, Luxiang Gan, Lei Feng, Ting Li, Yi Wang, Yu Fu, Lei Cai, Shao Li, Chao Yu, Yi Gao, Mingxin Pan, Shunjun Fu
Summary: This study reveals the role of a circular RNA molecule, circDHPR, in hepatocellular carcinoma (HCC). It affects tumor growth and metastasis by regulating the miR-3194-5p/RASGEF1B/Ras/MAPK signaling pathway, suggesting circDHPR as a potential biomarker and therapeutic target for HCC.
Article
Oncology
Long Bai, Xiao-Luan Yan, Yun-Xin Lu, Qi Meng, Yu-Ming Rong, Liu-Fang Ye, Zhi-Zhong Pan, Bao-Cai Xing, De-Shen Wang
Summary: The study aimed to develop a novel prognostic stratification tool for colorectal cancer liver metastasis (CRLM) resection. The CLIR score outperformed the Fong score in predicting long-term survival of CRC patients after complete hepatic resection, with five independent predictors associated with worse overall survival identified.
ANNALS OF SURGICAL ONCOLOGY
(2022)