韦穆拉菲尼布激活了声波刺通路,并促进了甲状腺癌干细胞自我更新
Yurong Lu1, Yuqing Zhao1, Penggang Liu1
1Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China.
Endocrine-related cancer
|August 29, 2023
概括
韦穆拉芬尼 (PLX4032) 通过激活声波刺通路,增加了甲状腺癌癌干细胞活性. 将维穆拉费尼布与Gli1抑制剂结合,可以克服这种抗药性,提高治疗效率.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- B-Raf激酶抑制剂在BRAF突变的甲状腺癌中表现出有限的疗效.
- 癌症干细胞 (CSCs) 与瘤复发和耐药性有关.
研究的目的:
- 研究CSCs在甲状腺癌中B-Raf激酶抑制剂有限疗效中的作用.
- 阐明维穆拉芬尼 (vemurafenib) 影响CSCs的机制,并探索组合疗法.
主要方法:
- 用维穆拉费尼布 (PLX4032) 治疗形甲状腺癌细胞系 (SW1736,8505C) 和黑色素瘤细胞 (A375) .
- 评估与干细胞相关的基因表达 (Gli1,牛,BMI1,SOX2) 和CSC自我更新标记物 (ALDH阳性细胞,甲状腺球).
- 研究信号通路 (PI3K,MAPK,HER3,Shh) 和结合治疗Gli1抑制剂 (GANT61) 在体外和体内异种移植模型.
主要成果:
- 韦穆拉菲尼布诱导了干性基因,并促进了CSC在甲状腺癌细胞中的自我更新,但不是在黑色素瘤细胞中.
- 从机理上讲,维穆拉费尼布通过HER3激活PI3K/MAPK通路,从而导致Gli1交叉激活.
- 通过GANT61抑制Gli1阻断了干性基因表达,并在组合治疗中增强了vemurafenib的抗瘤活性.
结论:
- 甲状腺癌对B-Raf抑制剂的不良反应与通过声波刺通路的CSC激活有关.
- 结合B-Raf和Shh通路的向提供了一个有希望的策略,以克服甲状腺癌的耐药性.
关键词:
Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1 Gli1PLX4032 的时间.癌症干细胞是癌症干细胞.声波刺是一种刺.甲状腺癌是一种癌症.
相关概念视频
02:40Cancer Stem Cells and Tumor Maintenance
5.0K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.0K
01:06Induced Pluripotent Stem Cells
4.2K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.2K
02:38Mitogens and the Cell Cycle
6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
02:23Abnormal Proliferation
4.6K
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...
4.6K
03:03mTOR 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
02:33Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K