MUC13 drives cancer aggressiveness and metastasis through the YAP1-dependent pathway

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 MUC1 3 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.

Automated summary

This study reveals the role of MUC1 3 in survival and distant metastasis of colorectal cancer cells. MUC1 3 targets and activates YAP1, promoting its nuclear translocation and increasing the expression of pro-survival and metastasis-associated genes. The correlation between MUC1 3 and YAP1 expression was observed in animal models and human colorectal cancer tissues.