| 项目编号: | 1511357
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| 项目名称: | UNS:Metabolic Reprogramming of Colon Cancer Metastasis |
| 作者: | Xiling Shen
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| 承担单位: | Cornell University
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| 批准年: | 2014
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| 开始日期: | 2015-09-15
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| 结束日期: | 2018-08-31
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| 资助金额: | USD350000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | colon
; study
; human crc
; colorectal cancer
; colon cancer patient
; primary cancer cell
; cancer-related death
; xilingcolon cancer
; metastatic colon cancer patient
; crc metastasis research
; metastatic tumor
; colon cancer metastasis
; metabolic state
; crc metastasis
; cancer cell
; metastatic reprogramming
; chemokine-targeting metastasis model
; anti-metastasis therapy
; metastatic colon cancer cell
; cancer death
; colon cancer cell
; metastatic cancer cell
; metabolic reprogramming
|
| 英文摘要: | 1511357
Shen, Xiling
Colon cancer is a leading cause of cancer death. Current chemotherapies are rather ineffective once tumor cells metastasize, spreading from colon to other organs. This study aims to understand whether metastatic colon cancer cells are influenced by their new environments, and whether they change their metabolic states when growing outside the colon. The metabolic states of colon cancer cells in different organs will be systematically characterized and compared. Regulatory pathways involved in metabolic state alteration will be identified and further validated by clinical data from colon cancer patients. These pathways will then be targeted therapeutically to suppress metastatic tumor growth or sensitize them to conventional chemotherapy. If successful, this study will contribute to advancing national health and enable new therapies that are specifically against colon cancer metastasis, and improve the survival and life quality of metastatic colon cancer patients.
Metastasis of cancer cells from primary sites to distant organs is a major cause of cancer-related death, as current chemotherapies are largely ineffective against metastases. However, whether and how metastatic cancer cells might behave differently from primary cancer cells remains largely unclear. This project aims to test whether colorectal cancer (CRC) metastases undergo metabolic reprogramming and whether altered metabolism may contribute to malignancy and chemoresistance of metastatic tumors. This study will take advantage of innovative CRC models developed by the PI's lab. The chemokine-targeting metastasis model (CTMM) recapitulates the anatomical route of human CRC metastasis, while the blastocyst-injection chimeric model (BICM) allows immunoproficient mice to grow human CRC without immunorejection. Primary and metastatic tumors from those models will be profiled by transcriptomics and metabolomics. Integrated network analysis of the transcriptome and metabolome will identify altered pathways in CRC metastases. The findings will be corroborated by a large CRC metastases sample collection. Anti-metastasis therapy targeting metastatic reprogramming will be evaluated. Enzymes and metabolites can be targeted by shRNA, small molecule inhibitors, and dietary restrictions. This new strategy has the potential to outperform or synergize with current frontline chemotherapy against CRC metastasis. Furthermore, this proposal also addresses a roadblock for CRC metastasis research and drug discovery, which is the lack of a model that recapitulates human CRC. CTMM and BICM will allow researchers to study CRC and test drugs in relevant microenvironments.
This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/93284
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| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
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| Recommended Citation: | |
Xiling Shen. UNS:Metabolic Reprogramming of Colon Cancer Metastasis. 2014-01-01.
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