Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR.

Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR.
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DOI:
10.1007/s00418-023-02183-8
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发表时间:
2023-06
影响因子:
2.3
通讯作者:
--
中科院分区:
生物学3区
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细胞内吞作用是细胞摄取大分子的重要过程,在肿瘤中被认为是一种失调现象。网格蛋白和小窝蛋白-1在受体介导的内吞作用中起主要作用。我们已经使用了一种定量的、无偏的和半自动化的方法来测量网格蛋白和小窝蛋白-1在癌性和配对的正常(癌相邻的、非癌的)人前列腺组织中的原位蛋白表达。与正常组织(N = 29,n = 67)相比,前列腺癌样品(N = 29,n = 91)中网格蛋白的表达显著(p < 0.0001)增加(N =患者数量,n =组织阵列中的核心数量)。相反,与正常前列腺组织相比,前列腺癌组织中小窝蛋白-1的表达显著降低(p < 0.0001)。这两种蛋白表达的相反变化与癌症侵袭性的增加高度相关。在前列腺癌组织中,表皮生长因子受体(EGFR)(癌发生中的关键受体)的表达与网格蛋白同时增加,表明EGFR通过网格蛋白介导的内吞作用(CME)再循环。这些结果表明,在前列腺癌中,小窝蛋白-1介导的内吞作用(CavME)可能起制动作用,CME的增加可能通过EGFR的再循环促进前列腺癌的致瘤性和侵袭性。这些蛋白质表达的变化也可能用作前列腺癌的生物标志物,以帮助诊断和预后以及临床决策。在线版本包含补充材料,可通过10.1007/s 00418 -023-02183-8获得。
Endocytosis, an important macromolecule uptake process in cells, is known to be dysregulated in cancer. Clathrin and caveolin-1 proteins play a major role in receptor-mediated endocytosis. We have used a quantitative, unbiased and semi-automated method to measure in situ protein expression of clathrin and caveolin-1 in cancerous and paired normal (cancer adjacent, non-cancerous) human prostate tissue. There was a significant (p < 0.0001) increase in the expression of clathrin in prostate cancer samples (N = 29, n = 91) compared to normal tissue (N = 29, n = 67) (N = number of patients, n = number of cores in tissue arrays). Conversely, there was a significant (p < 0.0001) decrease in expression of caveolin-1 in prostate cancer tissue compared to normal prostate tissue. The opposite change in expression of the two proteins was highly correlated to increasing cancer aggressiveness. There was also a concurrent increase in the expression of epidermal growth factor receptor (EGFR), a key receptor in carcinogenesis, with clathrin in prostate cancer tissue, indicating recycling of EGFR through clathrin-mediated endocytosis (CME). These results indicate that in prostate cancer, caveolin-1-mediated endocytosis (CavME) may be acting as a brake and increase in CME may facilitate tumorigenicity and aggressiveness of prostate cancer through recycling of EGFR. Changes in the expression of these proteins can also potentially be used as a biomarker for prostate cancer to aid in diagnosis and prognosis and clinical decision-making. The online version contains supplementary material available at 10.1007/s00418-023-02183-8.
参与前列腺癌变的分子途径:公共微阵列数据集的见解。
DOI: 10.1371/journal.pone.0049831
发表时间: 2012
期刊: PloS one
影响因子: 3.7
作者:
Baetke SC;Adriaens ME;Seigneuric R;Evelo CT;Eijssen LM
通讯作者: Eijssen LM
DOI: 10.1371/journal.pone.0124395
发表时间: 2015
期刊: PloS one
影响因子: 3.7
作者:
Arya M;Thrasivoulou C;Henrique R;Millar M;Hamblin R;Davda R;Aare K;Masters JR;Thomson C;Muneer A;Patel HR;Ahmed A
通讯作者: Ahmed A