Figure 9: Proposed working model of GALNT14-mediated lung-specific metastasis of breast cancer. | Nature Communications

Figure 9: Proposed working model of GALNT14-mediated lung-specific metastasis of breast cancer.

From: GALNT14 promotes lung-specific breast cancer metastasis by modulating self-renewal and interaction with the lung microenvironment

Figure 9

Left: the KRAS-PI3K pathway, which is activated in BCCs with high lung-metastatic potential, induces the c-JUN-mediated transcriptional upregulation of GALNT14. GALNT14-expressing BCCs possess the ability to self-renew against lung-derived BMPs, potentially via GALNT14-mediated BMPR O-GalNAcylation, which results in the attenuation of BMP responsiveness and therefore an increase in SOX4 expression. As a result, GALNT14-expressing BCCs can initiate metastatic colonies in the lung parenchyma. Right: To establish macrometastases, GALNT14-expressing BCCs secrete chemokines, which creates a favourable microenvironment by stimulating macrophage infiltration. Furthermore, the O-GalNAcylation of FGFR1 by GALNT14 enables BCCs to exploit macrophage-derived FGFs (for example, FGF2), ensuring their continuous proliferation within the lung microenvironment.

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