功能失调的脂肪细胞通过依赖YAP/TAZ的癌症相关的脂肪细胞转化促进瘤进展
Yaechan Song1, Heeju Na1, Seung Eon Lee1
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Nature communications
|May 14, 2024
概括
肥胖通过改变瘤微环境 (TME) 内的脂肪细胞 (脂肪细胞) 来促进癌症. 针对功能障碍脂肪细胞中的YAP/TAZ信号,可以抑制瘤生长,提供一种新的癌症治疗方法.
科学领域:
- 在瘤学瘤学.
- 代谢性疾病 代谢性疾病
- 细胞生物学 细胞生物学
背景情况:
- 肥胖是各种癌症的重要危险因素.
- 脂肪细胞在瘤微环境 (TME) 中的确切作用及其与肥胖驱动的癌症的联系仍然不清楚.
- 癌症相关脂肪细胞 (CAAs) 参与促进瘤进展.
研究的目的:
- 研究CAA的形成及其对瘤生长的贡献.
- 阐明功能障碍脂肪细胞和YAP/TAZ信号在与肥胖有关的癌症中的作用.
- 评估位脂肪细胞平衡的治疗潜力.
主要方法:
- 使用了表脂细胞特异性BECN1淘汰 (BaKO) 的小鼠,表现出脂质营养不良.
- 分析了CAAs和BECN1-缺乏脂肪细胞中的YAP/TAZ信号激活.
- 研究了高脂肪饮食 (HFD) 和YAP/TAZ抑制 (脊椎蛋白) 对瘤生长的影响.
主要成果:
- 功能失调的脂肪细胞激活了YAP/TAZ信号,导致脱差和恶性TME.
- 在BaKO小鼠中删除YAP/TAZ逆转了脂质和炎症,导致瘤回归.
- 用HFD养的小鼠显示BECN1降低和YAP/TAZ增加; 脊素治疗抑制了瘤生长.
结论:
- YAP/TAZ信号是CAA形成和TME发展的关键媒介.
- 准脂肪细胞功能障碍和YAP/TAZ信号提供了一个有前途的策略,用于治疗肥胖个体的癌症.
- 恢复脂肪细胞平衡可能是抑制癌症生长的可行方法.
相关概念视频
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Adaptive Mechanisms in Cancer Cells
5.7K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K


