Colorectal Cancer Transcriptome: Effects of Genomic Instability and Aneuploidy

结直肠癌转录组：基因组不稳定性和非整倍性的影响

• 批准号: 10702420
• 负责人: Thomas Ried
• 金额: $ 74.51万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702420
• 关键词: Address; Aneuploidy; Biological; Cataloging; Cell Cycle; Cell Proliferation; Cells; Clinical; Clone Cells; Colon Carcinoma; Colorectal; Colorectal Cancer; Complex; Critical Pathways; Development; Diagnosis; EGF gene; Environment; Exposure to; Fluorescence-Activated Cell Sorting; Fluorouracil; Foundations; Gene Expression; Gene Silencing; Genes; Genetic; Genome; Genomic Instability; Goals; Growth; Individual; Intestines; Malignant - descriptor; Malignant Neoplasms; Mediating; Methods; Modification; Mutation; Mutation Analysis; Neoplasm Metastasis; Pathway interactions; Patients; Pattern; Phenotype; Process; RNA Interference; Radiation; Rectal Cancer; S phase; Signal Pathway; Signal Transduction; Small Interfering RNA; Solid Neoplasm; Specimen; Stimulus; Stress; Technology; Testing; Therapeutic; Transforming Growth Factor beta; WNT Signaling Pathway; Xenograft procedure; base; cancer cell; chemoradiation; clinically relevant; colon cancer cell line; colon tumorigenesis; deep sequencing; evidence base; fitness; functional genomics; gene function; insight; intestinal epithelium; knock-down; neoplastic cell; novel; overexpression; promoter; response; screening; small hairpin RNA; stem cell niche; stem cells; targeted treatment; therapy resistant; tool; transcriptome; treatment response; tumor; tumor heterogeneity; tumorigenesis

In a review this year, we summarized the "Shifting the Focus of Signaling Abnormalities in Colon Cancer". Colon cancer tumorigenesis occurs incrementally. The process involves the acquisition of mutations which typically follow an established pattern: activation of WNT signaling, activation of RAS signaling, and inhibition of TGF-beta signaling. This arrangement recapitulates, to some degree, the stem cell niche of the intestinal epithelium, which maintains WNT and EGF activity while suppressing TGF-beta. The resemblance between the intestinal stem cell environment and colon cancer suggests that the concerted activity of these pathways generates and maintains a potent growth-inducing stimulus. However, each pathway has a myriad of downstream targets, making it difficult to identify which aspects of these pathways are drivers. To address this, we utilize the cell cycle, the ultimate regulator of cell proliferation, as a foundation for cross-pathway integration. We attempt to generate an overview of colon cancer signaling patterns by integrating the major colon cancer signaling pathways in the context of cell replication, specifically, the entrance from G1 into S-phase.

在今年的综述中，我们总结了“结肠癌信号异常的重点”。结肠癌肿瘤发生逐渐发生。该过程涉及通常遵循建立模式的突变的获取：Wnt信号的激活，RAS信号的激活以及TGF-beta信号传导的抑制。这种布置在某种程度上概括了肠上皮的干细胞细胞生态位，在抑制TGF-beta的同时，它保持了Wnt和EGF活性。肠道干细胞环境与结肠癌之间的相似之处表明，这些途径的一致活性产生并保持有效的生长刺激。但是，每个途径都有无数的下游目标，因此很难确定这些途径的哪些方面是驱动因素。为了解决这个问题，我们利用细胞周期（细胞增殖的最终调节剂）作为跨道路整合的基础。我们试图通过在细胞复制的背景下，特别是从G1进入S期的入口来概述结肠癌信号传导模式的概述。

项目成果

Correction to: Rb inactivation accelerates neoplastic growth and substitutes for recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated with p53 deficiency.

更正：在与 p53 缺陷相关的散发性乳腺癌中，Rb 失活会加速肿瘤生长并替代 cIAP1、cIAP2 和 Yap1 的反复扩增。

• DOI: 10.1038/s41388-021-01647-2
• 发表时间: 2021
• 期刊: Oncogene
• 影响因子: 8
• 作者: Cheng,L;Zhou,Z;Flesken-Nikitin,A;Toshkov,IA;Wang,W;Camps,J;Ried,T;Nikitin,AY
• 通讯作者: Nikitin,AY

Genetic amplification of the NOTCH modulator LNX2 upregulates the WNT/β-catenin pathway in colorectal cancer.

• DOI: 10.1158/0008-5472.can-12-3159
• 发表时间: 2013-03-15
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Camps J;Pitt JJ;Emons G;Hummon AB;Case CM;Grade M;Jones TL;Nguyen QT;Ghadimi BM;Beissbarth T;Difilippantonio MJ;Caplen NJ;Ried T
• 通讯作者: Ried T

Trichostatin A preferentially reverses the upregulation of gene-expression levels induced by gain of chromosome 7 in colorectal cancer cell lines.

• DOI: 10.1002/gcc.22505
• 发表时间: 2018-01
• 期刊: Genes, chromosomes & cancer
• 作者: Buishand FO;Cardin E;Hu Y;Ried T
• 通讯作者: Ried T

Preoperative chemoradiotherapy in locally advanced rectal cancer: correlation of a gene expression-based response signature with recurrence.

• DOI: 10.1016/j.cancergencyto.2008.11.011
• 发表时间: 2009-04-15
• 期刊: Cancer genetics and cytogenetics
• 作者: Liersch T;Grade M;Gaedcke J;Varma S;Difilippantonio MJ;Langer C;Hess CF;Becker H;Ried T;Ghadimi BM
• 通讯作者: Ghadimi BM

Chromosome mis-segregation and cytokinesis failure in trisomic human cells.

• DOI: 10.7554/elife.05068
• 发表时间: 2015-05-05
• 期刊: eLife
• 影响因子: 7.7
• 作者: Nicholson JM;Macedo JC;Mattingly AJ;Wangsa D;Camps J;Lima V;Gomes AM;Dória S;Ried T;Logarinho E;Cimini D
• 通讯作者: Cimini D