Key Laboratory of Precision Oncology in Universities of Shandong, Institute of Precision Medicine, Jining Medical University, Jining, China.
Department of General Surgery, Affiliated Hospital of Jining Medical University, Jining, China.
Cancer Sci. 2022 Sep;113(9):3018-3031. doi: 10.1111/cas.15432. Epub 2022 Jun 14.
Previous studies have reported that TIFA plays different roles in various tumor types. However, the function of TIFA in colorectal cancer (CRC) remains unclear. Here, we showed that the expression of TIFA was markedly increased in CRC versus normal tissue, and positively correlated with CRC TNM stages. In agreement, we found that the CRC cell lines show increased TIFA expression levels versus normal control. The knockdown of TIFA inhibited cell proliferation but had no effect on cell apoptosis in vitro or in vivo. Moreover, the ectopic expression of TIFA enhanced cell proliferation ability in vitro and in vivo. In contrast, the expression of mutant TIFA (T9A, oligomerization site mutation; D6, TRAF6 binding site deletion) abolished TIFA-mediated cell proliferation enhancement. Exploration of the underlying mechanism revealed that the protein synthesis-associated kinase RSK and PRAS40 activation were responsible for TIFA-mediated CRC progression. In summary, these findings suggest that TIFA plays a role in mediating CRC progression. This could provide a promising target for CRC therapy.
先前的研究报告表明，TIFA 在不同类型的肿瘤中发挥不同的作用。然而，TIFA 在结直肠癌（CRC）中的功能尚不清楚。在这里，我们发现 TIFA 在 CRC 与正常组织中的表达明显增加，并且与 CRC TNM 分期呈正相关。一致地，我们发现 CRC 细胞系的 TIFA 表达水平相对于正常对照增加。TIFA 的敲低抑制了体外和体内的细胞增殖，但对细胞凋亡没有影响。此外，TIFA 的异位表达增强了体外和体内的细胞增殖能力。相比之下，表达突变型 TIFA（T9A，寡聚化位点突变；D6，TRAF6 结合位点缺失）则消除了 TIFA 介导的细胞增殖增强作用。对潜在机制的探索表明，与蛋白合成相关的激酶 RSK 和 PRAS40 的激活是 TIFA 介导的 CRC 进展的原因。总之，这些发现表明 TIFA 在介导 CRC 进展中发挥作用。这可能为 CRC 治疗提供一个有前途的靶点。
