Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Korea.
Cell Death Dis. 2022 Apr 29;13(4):417. doi: 10.1038/s41419-022-04862-1.
Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell-cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC.
结直肠癌（CRC）的 5 年生存率<10%，因为它可以转移到肺部和肝脏。用于治疗转移性结直肠癌的抗癌药物和靶向疗法的治疗效果不足，并且与并发症相关。因此，有必要研究开发新的靶向治疗方法。在这里，我们提出了一个新的发现，即细胞间黏附分子-1（ICAM-1）是增强结直肠癌治疗效果的潜在治疗靶标。ICAM-1 是细胞间相互作用的重要调节剂，最近的研究表明它促进了几种癌的恶性程度。然而，关于它对 CRC 的影响知之甚少。因此，我们进行了一项研究来确定 ICAM-1 发挥作用的机制。ICAM-1 被酪氨酸蛋白激酶 Met（c-MET）磷酸化，磷酸化的 ICAM-1 可以与 SRC 相互作用以增加 SRC 活性。因此，ICAM-1 可能进一步加速 SRC 信号转导，促进癌症的恶性潜力。此外，用针对 ICAM-1 的抗体治疗显示出减少转移和血管生成的优异治疗效果。这些发现首次表明，ICAM-1 是一种能够介导 c-MET-SRC 信号轴的重要衔接蛋白。因此，ICAM-1 可作为结直肠癌的新型治疗靶标和转移标志物。
