TP53INP2 modulates the malignant progression of colorectal cancer by reducing the inactive form of β-catenin
TP53INP2 modulates the malignant progression of colorectal cancer by reducing the inactive form of β-catenin
复制标题
DOI：
10.1016/j.bbrc.2023.149275
复制
发表时间：
2023-11-22
影响因子：
3.1
通讯作者：
Xu，Qiang
中科院分区：
文献类型：
--
作者：
Shi，Ke;Shan，Yunlong;Xu，Qiang
TP 53 INP 2（肿瘤蛋白p53诱导核蛋白2），被称为自噬蛋白，是调节转录和饥饿诱导的自噬所必需的，其在各种癌症的发生和进展中起着至关重要的作用。本研究旨在探讨TP 53 INP 2在结直肠癌中的表达模式、功能及预后价值。在此，我们报道了TP 53 INP 2的低表达与结直肠癌患者的生存率低相关。与癌旁组织相比，TP 53 INP 2在结直肠癌组织中表达显著下调。随着大肠癌恶性程度的加重，TP 53 INP 2的表达水平逐渐降低。TP 53 INP 2的敲低促进小鼠中CRC细胞增殖和肿瘤生长。从机制上讲，TP 53 INP 2缺陷减少了β-连环蛋白在S33、S37和T41上的磷酸化，导致β-连环蛋白的积累增加，核转位和转录活性增强。此外，我们进一步证明TP 53 INP 2隔离TIM 50，从而抑制其对β-连环蛋白的激活。总之，我们的研究结果表明，下调TP 53 INP 2通过激活β-catenin促进CRC进展，并表明TP 53 INP 2可能是CRC的候选治疗靶点。
TP53INP2 (tumor protein p53-inducible nuclear protein 2), known as an autophagy protein, is essential for regulating transcription and starvation-induced autophagy, which plays a crucial role in the oncogenesis and progression of various cancers. The present study aims to investigate the expression pattern, function and prognostic value of TP53INP2 in colorectal cancer (CRC). Here, we report that low expression of TP53INP2 correlates with poor survival in CRC patients. TP53INP2 was significantly downregulated in CRC tissues compared with adjacent tissues. As the malignancy of CRC progresses, the expression level of TP53INP2 gradually decreased. Knockdown of TP53INP2 promoted CRC cell proliferation and tumor growth in mice. Mechanistically, TP53INP2 deficiency decreased phosphorylation of β-catenin on S33, S37, and T41, resulting in increased accumulation of β-catenin and enhanced nuclear translocation and transcriptional activity. Moreover, we further demonstrated that TP53INP2 sequestered TIM50, thereby inhibiting its activation of β-catenin. Taken together, our findings indicate that the downregulation of TP53INP2 promotes CRC progression by activating β-catenin and suggest that TP53INP2 may be a candidate therapeutic target for CRC.