Article
Biochemistry & Molecular Biology
Xiao-Shun He, Wen-Long Ye, Yu-Juan Zhang, Xiao-Qin Yang, Feng Liu, Jing-Ru Wang, Xiao-Lu Ding, Yun Yang, Ruo-Nan Zhang, Yuan-Yuan Zhao, Hai-Xia Bi, Ling-Chuan Guo, Wen-Juan Gan, Hua Wu
Summary: In this study, we found that BEST4 promotes cell proliferation and metastasis in colorectal cancer. It activates the Akt signaling pathway by binding to the regulatory subunit p85 alpha of PI3K, leading to the expression of critical regulators such as MYC and CCND1. Additionally, high expression of BEST4 is associated with poor prognosis in patients.
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.
Review
Biochemistry & Molecular Biology
Gongmin Zhu, Lijiao Pei, Hongwei Xia, Qiulin Tang, Feng Bi
Summary: KRAS is a commonly mutated oncogene in colorectal cancer, leading to aberrant activation of the KRAS protein and stimulation of downstream signaling pathways, resulting in cell proliferation and survival, ultimately leading to tumorigenesis. Patients with KRAS mutations in CRC have poor prognosis.
Article
Biochemistry & Molecular Biology
Peter F. Doubleday, Luca Fornelli, Ioanna Ntai, Neil L. Kelleher
Summary: The study highlights the significant role of KRAS mutations in colorectal cancer, particularly the upregulation of aspartate metabolizing proteins by KRAS(G13D) expression. Additionally, an increase in urea cycle enzymes expression was observed in tumor tissues. Expression of ASS1 promotes colorectal cancer cell proliferation, and high levels of various metabolites can rescue the loss of ASS1.
Article
Oncology
Asimina Koulouridi, Michaela Karagianni, Ippokratis Messaritakis, Maria Sfakianaki, Alexandra Voutsina, Maria Trypaki, Maria Bachlitzanaki, Evangelos Koustas, Michalis Karamouzis, Anastasios Ntavatzikos, Anna Koumarianou, Nikolaos Androulakis, Dimitrios Mavroudis, Maria Tzardi, John Souglakos
Summary: The study reveals that KRAS G12D mutation is associated with better overall survival, while KRAS G12C mutation may indicate worse prognosis in terms of progression-free and overall survival. KRAS exon 3 and exon 4 mutations also have different impacts on progression-free and overall survival.
Review
Cell Biology
Anabela Ferreira, Flavia Pereira, Celso Reis, Maria Jose Oliveira, Maria Joao Sousa, Ana Preto
Summary: KRAS mutations play a crucial role in promoting cancer cell proliferation, inducing autophagy, and suppressing apoptosis, leading to drug resistance and poor prognosis.
Article
Biochemistry & Molecular Biology
Jiuna Zhang, Xiaoyu Jiang, Jie Yin, Shiying Dou, Xiaoli Xie, Ting Liu, Yijun Wang, Shuling Wang, Xue Zhou, Dongxuan Zhang, Huiqing Jiang
Summary: RNF141 plays an oncogenic role in colorectal cancer by upregulating KRAS activity, which promotes tumor growth, cell proliferation, migration, and apoptosis by interacting with KRAS to induce its activation and enrichment on the plasma membrane.
Article
Oncology
Jeeshan Jiffry, Thongthai Thavornwatanayong, Devika Rao, Elisha J. Fogel, Durvanand Saytoo, Rishika Nahata, Hillary Guzik, Imran Chaudhary, Titto Augustine, Sanjay Goel, Radhashree Maitra
Summary: The study revealed that Pelareorep can enhance its propagation and oncolytic effect in colorectal cancer cells by regulating autophagy-related genes and proteins.
CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Hema Adhikari, Walaa E. Kattan, Shivesh Kumar, Pei Zhou, John F. Hancock, Christopher M. Counter
Summary: The lipid composition of the plasma membrane plays a crucial role in defining the oncogenic function of KRAS, with the adapter protein EFR3A binding to active KRAS to recruit PI4KA and alter lipid composition. Disruption of EFR3A or PI4KA reduces oncogenic signaling and tumorigenesis, suggesting a potential therapeutic strategy for KRAS-mutant cancers.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Hyoun Wook Lee, Boram Song, Kyungneun Kim
Summary: The presence of a residual adenoma component in colorectal cancer is associated with a high frequency of KRAS mutation and indolent clinicopathological features. The discordance in the incidence of KRAS mutation between the adenoma and carcinoma components emphasizes the need to document the adenoma component in the pathology report and avoid including it in molecular testing samples.
Review
Pharmacology & Pharmacy
Robert Roskoski
Summary: RAS proteins play crucial roles in physiological signal transduction processes related to cell growth, division, and survival. RAS mutations, especially KRAS mutations, are common in various cancers, with potential implications for targeted therapy. Covalent modification of the KRAS C12 led to the discovery of a new pocket, facilitating the development of second-line treatment for KRAS(G12C)-mutant non-small cell lung cancer. Efforts are also being made to develop inhibitors targeting MAP kinase and PI3-kinase pathways as indirect RAS antagonists.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cell Biology
Thomas Sell, Christian Klotz, Matthias M. Fischer, Rosario Astaburuaga-Garcia, Susanne Krug, Jarno Drost, Hans Clevers, Christine Sers, Markus Morkel, Nils Bluethgen
Summary: Colorectal cancer progression is closely related to deregulation of intestinal differentiation trajectory. The sequential mutations of APC, KRAS, TP53, and SMAD4 enable oncogenic signaling and establish cancer hallmarks. Mass cytometry of isogenic human colon and patient-derived cancer organoids reveals a differentiation axis from normal to cancer states, shaped by the driver mutations. Cells along this axis can be influenced by subsequent mutations to promote or restrict stem cell properties. Nodes of the cancer cell signaling network remain coupled to the differentiation state. Single-cell RNA sequencing links protein signaling network to transcriptomic states with biological and clinical importance.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xin-Ke Yin, Yun-Long Wang, Fei Wang, Wei-Xing Feng, Shao-Mei Bai, Wan-Wen Zhao, Li-Li Feng, Ming-Biao Wei, Cao-Litao Qin, Fang Wang, Zhi-Li Chen, Hong-Jun Yi, Yan Huang, Pei-Yi Xie, Taewan Kim, Ying-Nai Wang, Jun-Wei Hou, Chia-Wei Li, Quentin Liu, Xin-Juan Fan, Mien-Chie Hung, Xiang-Bo Wan
Summary: Arginine methylation, catalyzed by PRMTs, plays a crucial role in CRC. Overexpression of NONO in CRC tissue is associated with poor prognosis. Methylation of NONO by PRMT1 at R251 promotes CRC growth and metastasis, indicating PRMT1 inhibition as a potential therapeutic strategy for CRC treatment.
Article
Oncology
Philip A. Philip, Ibrahim Azar, Joanne Xiu, Michael J. Hall, Andrew Eugene Hendifar, Emil Lou, Jimmy J. Hwang, Jun Gong, Rebecca Feldman, Michelle Ellis, Phil Stafford, David Spetzler, Moh'd M. Khushman, Davendra Sohal, A. Craig Lockhart, Benjamin A. Weinberg, Wafi k S. El-Deiry, John Marshall, Anthony F. Shields, W. Michael Korn
Summary: KRAS WT PDAC represents 10.7% of PDAC and is enriched with potential pathogenic drivers and better treatment prognosis. Identifying KRAS WT patients can expand therapeutic options in clinical practice.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Qing-Lan Li, Xiang Lin, Ya-Li Yu, Lin Chen, Qi-Xin Hu, Meng Chen, Nan Cao, Chen Zhao, Chen-Yu Wang, Cheng-Wei Huang, Lian-Yun Li, Mei Ye, Min Wu
Summary: This study analyzed active enhancers in colorectal cancer patients using genomics, transcriptomics, and epigenomics, identifying variant super-enhancer loci and KLF3 as a relevant transcription factor. The research provides important epigenomic resource and functional factors for epigenetic studies in colorectal cancer, shedding light on the role of super enhancers in regulating colorectal cancer tumorigenesis. Multiple key transcription factors in colorectal cancer were predicted with motif analysis and core regulatory circuitry analysis.
NATURE COMMUNICATIONS
(2021)