跳转至内容
Merck
CN
  • Targeting lysosome function causes selective cytotoxicity in VHL-inactivated renal cell carcinomas.

Targeting lysosome function causes selective cytotoxicity in VHL-inactivated renal cell carcinomas.

Carcinogenesis (2019-09-27)
Nadia Bouhamdani, Dominique Comeau, Alexandre Coholan, Kevin Cormier, Sandra Turcotte
摘要

The inactivation of the tumor suppressor gene, von Hippel-Lindau (VHL), has been identified as the earliest event in renal cell carcinoma (RCC) development. The loss of heterogeneity by chromosome 3p deletion followed by inactivating mutations on the second VHL copy are events present in close to 90% of patients. Our study illustrates a lysosomal vulnerability in VHL-inactivated RCC in vitro. By investigating the mechanism of action of the previously identified STF-62247, a small bioactive compound known for its selective cytotoxic properties towards VHL-defective models, we present the promising approach of targeting truncal-driven VHL inactivation through lysosome disruption. Furthermore, by analyzing the open platform for exploring cancer genomic data (cbioportal), we uncover the high alteration frequency of essential lysosomal and autophagic genes in sequenced biopsies from clear cell RCC patient primary tumors. By investigating lysosome physiology, we also identify VHL-inactivated cells' inability to maintain their lysosomes at the perinuclear localization in response to STF-62247-induced stress and accumulate cytoplasmic inclusion bodies in response to an inefficient lysosomal degradative capacity. Finally, by testing other known lysosomal-disrupting agents (LDAs), we show that these are selectively cytotoxic to cells lacking VHL functions. Our study builds a strong platform that could specifically link genetic clonal ccRCC evolution to lysosomal and trafficking vulnerabilities.

材料
货号
品牌
产品描述

Sigma-Aldrich
甲醛 溶液, for molecular biology, 36.5-38% in H2O
登录查看公司和协议定价
货号包装规格是否有货价格数量
25 mL
预计发货时间 March 17, 2025
详情...
CN¥481.10
4 x 25 mL
预计发货时间 March 17, 2025
详情...
CN¥610.90
500 mL
预计发货时间 March 17, 2025
详情...
CN¥834.06
Sigma-Aldrich
吩嗪硫酸甲酯
登录查看公司和协议定价
货号包装规格是否有货价格数量
500 mg
预计发货时间 March 17, 2025
详情...
CN¥311.30
1 g
预计发货时间 March 17, 2025
详情...
CN¥496.02
5 g
预计发货时间 March 17, 2025
详情...
CN¥2,294.10
10 g
请联系客服了解存货情况
新价格,新优惠!
CN¥3,406.95
25 g
预计发货时间 April 24, 2025
详情...
新价格,新优惠!
CN¥5,456.97
Sigma-Aldrich
XTT 钠盐, powder, BioReagent, suitable for cell culture
登录查看公司和协议定价
货号包装规格是否有货价格数量
100 mg
预计发货时间 March 17, 2025
详情...
CN¥3,630.17
Sigma-Aldrich
STF-62247, ≥98% (HPLC), solid
登录查看公司和协议定价
货号包装规格是否有货价格数量
5 mg
预计发货时间 April 10, 2025
详情...
新价格,新优惠!
CN¥1,202.56