通过ONECUT2驱动的ADAMTS14激活,通过Wnt通路增强结直肠癌的干细胞性
1Department of Oncology, People's Hospital of Chongqing Hechuan, No. 1366, Xi'er'an Avenue, Nanban Subdistrict, Hechuan District, Chongqing, 401520, China.
Human cell
|November 12, 2025
概括
这项研究揭示了ONECUT2如何通过激活ADAMTS14和Wnt通路来驱动结直肠癌 (CRC) 的干. 这一发现为CRC干预提供了一个新的分子点.
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:
- 结肠直肠癌 (CRC) 的进展与癌症的发展有关.
- 调节CRC干性的精确机制仍然不完全理解.
研究的目的:
- 为了阐明结直肠癌 (CRC) 的调节机制.
- 为了确定CRC干预的新分子标.
主要方法:
- 在CRC组织和细胞系中评估ADAMTS14表达.
- 进行了功能实验,以评估ADAMTS14在CRC干和球化中的作用.
- 调查了ONECUT2和ADAMTS14之间的监管关系.
- 分析了Wnt信号通路的激活.
主要成果:
- 在CRC中ADAMTS14的表达很高,与预后不佳相关.
- 通过激活Wnt通路,ADAMTS14增强了CRC细胞干细胞特征 (ALDH1A1,ALDH1A3,CD133) 和球化.
- 同样在CRC表达高且与预后不佳相关的ONECUT2直接激活了ADAMTS14转录.
结论:
- 一个新的ONECUT2/ADAMTS14/Wnt信号轴调节结直肠癌 (CRC) 的干度.
- 这个轴代表了针对CRC的治疗策略的潜在分子标.
相关概念视频
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
Canonical Wnt Signaling Pathway
10.4K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.4K
Non-Canonical Wnt Signaling Pathways
8.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K
Cancer Stem Cells and Tumor Maintenance
5.8K
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...
5.8K
mTOR Signaling and Cancer Progression
4.6K
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...
4.6K
Metastasis
6.3K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.3K


