Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea; Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju, Republic of Korea.
Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
Biochem Biophys Res Commun. 2014 Sep 26;452(3):858-64. doi: 10.1016/j.bbrc.2014.09.012. Epub 2014 Sep 10.
Thymosin β4 (Tβ4) is a 43-amino-acid peptide involved in many biological processes. However, the precise molecular signaling mechanism(s) of Tβ4 in cell invasion and migration remain unclear. In this study, we show that Tβ4 was significantly overexpressed in colorectal cancer tissues compared to adjacent normal tissues and high levels of Tβ4 were correlated with stage of colorectal cancer, and that Tβ4 expression was associated with morphogenesis and EMT. Tβ4-upregulated cancer cells showed increased adhesion, invasion and migration activity, whereas Tβ4-downregulated cells showed decreased activities. We also demonstrated that Tβ4 interacts with ILK, which promoted the phosphorylation and activation of AKT, the phosphorylation and inactivation of GSK3β, the expression and nuclear localization of β-catenin, and integrin receptor activation. These results suggest that Tβ4 is an important regulator of the ILK/AKT/β-catenin/Integrin signaling cascade to induce cell invasion and migration in colorectal cancer cells, and is a potential target for cancer treatment.
胸腺素 β4（Tβ4）是一种参与多种生物学过程的 43 个氨基酸肽。然而，Tβ4 在细胞侵袭和迁移中的精确分子信号机制尚不清楚。在这项研究中，我们发现 Tβ4 在结直肠癌组织中明显过表达，与相邻的正常组织相比，并且高水平的 Tβ4 与结直肠癌的分期相关，并且 Tβ4 的表达与形态发生和 EMT 相关。Tβ4 上调的癌细胞表现出增强的粘附、侵袭和迁移活性，而 Tβ4 下调的细胞表现出活性降低。我们还证明 Tβ4 与 ILK 相互作用，促进 AKT 的磷酸化和激活、GSK3β 的磷酸化和失活、β-catenin 的表达和核定位以及整合素受体的激活。这些结果表明，Tβ4 是诱导结直肠癌细胞侵袭和迁移的 ILK/AKT/β-catenin/Integrin 信号级联的重要调节剂，是癌症治疗的潜在靶点。
