https://ror.org/02p5xjf12 Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA.
https://ror.org/02p5xjf12 South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA.
Life Sci Alliance. 2023 Oct 4;6(12). doi: 10.26508/lsa.202301975. Print 2023 Dec.
Anchorage-independent survival after intravasation of cancer cells from the primary tumor site represents a critical step in metastasis. Here, we reveal new insights into how MUC13-mediated anoikis resistance, coupled with survival of colorectal tumor cells, leads to distant metastasis. We found that MUC13 targets a potent transcriptional coactivator, YAP1, and drives its nuclear translocation via forming a novel survival complex, which in turn augments the levels of pro-survival and metastasis-associated genes. High expression of MUC13 is correlated well with extensive macrometastasis of colon cancer cells with elevated nuclear YAP1 in physiologically relevant whole animal model systems. Interestingly, a positive correlation of MUC13 and YAP1 expression was observed in human colorectal cancer tissues. In brief, the results presented here broaden the significance of MCU13 in cancer metastasis via targeting YAP1 for the first time and provide new avenues for developing novel strategies for targeting cancer metastasis.
肿瘤细胞从原发肿瘤部位的浸润后，其独立于锚定的生存能力是转移的关键步骤。在这里，我们揭示了新的见解，即 MUC13 介导的失巢凋亡抗性与结直肠肿瘤细胞的存活如何导致远处转移。我们发现 MUC13 靶向一种有效的转录共激活因子 YAP1，并通过形成新的存活复合物使其核易位，从而增强了促生存和转移相关基因的水平。在生理相关的全动物模型系统中，MUC13 的高表达与结肠癌细胞的广泛大转移以及核 YAP1 的升高密切相关。有趣的是，在人结直肠癌组织中观察到 MUC13 和 YAP1 表达呈正相关。总之，这些结果首次通过靶向 YAP1 拓宽了 MUC13 在癌症转移中的意义，并为开发针对癌症转移的新策略提供了新途径。
