Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, 214062, Jiangsu, China.
Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China.
Med Oncol. 2024 Mar 27;41(5):100. doi: 10.1007/s12032-024-02349-x.
Colorectal cancer (CRC) ranks as the third most prevalent cancer type globally. Nevertheless, the fundamental mechanisms driving CRC progression remain ambiguous, and the prognosis for the majority of patients diagnosed at an advanced stage is dismal. YWHA/14-3-3 proteins serve as central nodes in several signaling pathways and are closely related to tumorigenesis and progression. However, their exact roles in CRC are still poorly elucidated. In this study, we revealed that YWHAG was the most significantly upregulated member of the YWHA/14-3-3 family in CRC tissues and was associated with a poor prognosis. Subsequent phenotypic experiments showed that YWHAG promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, RNA-seq data showed that multiple signaling pathways, including Wnt and epithelial-mesenchymal transition, were potentially regulated by YWHAG. CTTN was identified as a YWHAG-associated protein, and mediated its tumor-promoting functions by activating the Wnt/β-catenin signaling in CRC cells. In summary, our data indicate that YWHAG facilitates the proliferation, migration, and invasion of CRC cells by modulating the CTTN-Wnt/β-catenin signaling pathway, which offers a novel perspective for the treatment of CRC.
结直肠癌（CRC）是全球第三大常见癌症类型。然而，驱动 CRC 进展的基本机制仍不清楚，大多数在晚期诊断的患者的预后较差。YWHA/14-3-3 蛋白作为几种信号通路的中心节点，与肿瘤发生和进展密切相关。然而，它们在 CRC 中的具体作用仍不清楚。在这项研究中，我们揭示了 YWHAG 是 CRC 组织中 YWHA/14-3-3 家族中上调最显著的成员，与预后不良相关。随后的表型实验表明，YWHAG 促进了 CRC 细胞的增殖、迁移和侵袭。从机制上讲，RNA-seq 数据表明，包括 Wnt 和上皮-间充质转化在内的多种信号通路可能受到 YWHAG 的调节。CTTN 被鉴定为 YWHAG 相关蛋白，并通过激活 CRC 细胞中的 Wnt/β-catenin 信号通路来介导其促肿瘤功能。总之，我们的数据表明，YWHAG 通过调节 CTTN-Wnt/β-catenin 信号通路促进 CRC 细胞的增殖、迁移和侵袭，为 CRC 的治疗提供了新的视角。
