The TIP60-CD44 Axis Modulates Colorectal Cancer Stemness.

IF 5.1 2区生物学 Q2 CELL BIOLOGY

Cells Pub Date : 2025-05-09 DOI:10.3390/cells14100686

Asad Mohammad, Sudhakar Jha

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引用次数: 0

Abstract

HIV-1 Tat-interactive protein of 60 kDa (TIP60) is a lysine acetyltransferase protein that can acetylate histone and non-histone proteins. This study highlights TIP60's role in regulating colorectal cancer (CRC) stemness. The depletion of TIP60 resulted in a marked decrease in cellular proliferation, highlighting TIP60's involvement in the progression of CRC. Additionally, the loss of TIP60 impacted colony formation, transitioning from densely packed structures to dispersed spindle networks along with the loss of E-cadherin, indicating its role in the epithelial-mesenchymal transition (EMT). Three-dimensional culture models suggest that TIP60 is vital for spheroid formation, highlighting its importance in maintaining cancer stem cell properties in CRC. TIP60-depleted cells showed increased invasion in a 3D basement membrane extract (BME) invasion matrix, demonstrating its essential role in cellular invasiveness. Mechanistically, the reduction of TIP60 resulted in a decrease in CD44 expression, a critical marker for cancer stem cells (CSCs). Notably, CD44 overexpression restored the efficiency of spheroid formation and cell proliferation while reversing the EMT phenotype. Developing the TIP60-CD44 axis as a therapeutic target to treat CRC stemness and metastasis will help decrease the burden due to the deadly disease.

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TIP60-CD44轴调控结直肠癌干性

60 kDa的HIV-1 tat互作蛋白（TIP60）是一种赖氨酸乙酰转移酶蛋白，可使组蛋白和非组蛋白乙酰化。这项研究强调了TIP60在调节结直肠癌（CRC）发生中的作用。TIP60的缺失导致细胞增殖明显减少，强调了TIP60参与CRC的进展。此外，TIP60的缺失影响了集落的形成，随着e -钙粘蛋白的缺失，集落从密集排列的结构转变为分散的纺锤体网络，表明其在上皮-间质转化（EMT）中的作用。三维培养模型表明TIP60对于球形细胞的形成至关重要，强调了其在维持CRC中癌症干细胞特性中的重要性。tip60缺失的细胞在3D基底膜提取物（BME）侵袭基质中表现出侵袭性增加，表明其在细胞侵袭中起重要作用。从机制上讲，TIP60的减少导致CD44表达的减少，CD44是癌症干细胞（CSCs）的关键标志物。值得注意的是，CD44过表达恢复了球体形成和细胞增殖的效率，同时逆转了EMT表型。开发TIP60-CD44轴作为治疗结直肠癌干性和转移的治疗靶点，将有助于减轻这种致命疾病带来的负担。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

9.90

自引率

5.00%

发文量

3472

审稿时长

16 days

期刊介绍： Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.