Egusquiza-Alvarez Carlos Alejandro, Castañeda-Patlán M Cristina, Albarran-Gutierrez Sara, Gonzalez-Aguilar Héctor, Moreno-Londoño Angela P, Maldonado Vilma, Melendez-Zajgla Jorge, Robles-Flores Martha
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
Epigenetics and Functional Genomics Laboratories, National Institute of Genomic Medicine, Mexico City, Mexico.
Front Oncol. 2021 May 31;11:642940. doi: 10.3389/fonc.2021.642940. eCollection 2021.
p32 is a multifunctional and multicompartmental protein that has been found upregulated in numerous adenocarcinomas, including colorectal malignancy. High levels of p32 expression have been correlated with poor prognosis in colorectal cancer. However, the functions performed by p32 in colorectal cancer have not been characterized. Here we show that p32 is overexpressed in colorectal cancer cell lines compared to non-malignant colon cells. Colon cancer cells also display higher nuclear levels of p32 than nuclear levels found in non-malignant cells. Moreover, we demonstrate that p32 regulates the expression levels of genes tightly related to malignant phenotypes such as and . Remarkably, we demonstrate that knockdown of p32 negatively affects Akt/mTOR signaling activation, inhibits the migration ability of colon malignant cells, and sensitizes them to cell death induced by oxidative stress and chemotherapeutic agents, but not to cell death induced by nutritional stress. In addition, knockdown of p32 significantly decreased clonogenic capacity and tumorigenesis in a xenograft mice model. Altogether, our results demonstrate that p32 is an important promoter of malignant phenotype in colorectal cancer cells, suggesting that it could be used as a therapeutic target in colorectal cancer treatment.
p32是一种多功能且存在于多个细胞区室的蛋白质，已发现在包括结直肠癌在内的多种腺癌中表达上调。p32的高表达与结直肠癌的不良预后相关。然而，p32在结直肠癌中所发挥的功能尚未明确。在此我们表明，与非恶性结肠细胞相比，p32在结肠癌细胞系中过表达。结肠癌细胞中p32的核水平也高于非恶性细胞中的核水平。此外，我们证明p32调节与恶性表型紧密相关的基因的表达水平，如[此处原文缺失相关基因名称]和[此处原文缺失相关基因名称]。值得注意的是，我们证明敲低p32会对Akt/mTOR信号激活产生负面影响，抑制结肠恶性细胞的迁移能力，并使它们对氧化应激和化疗药物诱导的细胞死亡敏感，但对营养应激诱导的细胞死亡不敏感。此外，在异种移植小鼠模型中，敲低p32显著降低了克隆形成能力和肿瘤发生。总之，我们的结果表明p32是结肠癌细胞恶性表型的重要促进因子，提示它可作为结直肠癌治疗的一个治疗靶点。
