Overall, these data show that the interplay between hypoxia and matrix stress relaxation amplifies PLOD2, which in turn accelerates sarcoma cell motility and metastasis.
In summary, our findings revealed a new stromal collagen network that favors tumor invasion and metastasis establish between breast cancer cells and surrounding adipocytes at the tumor invasive front, and identified PLOD2 as a therapeutic target for metastatic breast cancer treatment.
High levels of LH2 have been reported in the formation and stabilization of hydroxylysine aldehyde-derived collagen cross-links (HLCCs), leading to fibrosis and cancer metastasis in certain tissues.
Gain- and loss-of-function studies and orthotopic implantation metastasis model pinpointed that PLOD2 promotes NSCLC metastasis directly by enhancing migration and indirectly by inducing collagen reorganization.
Among the identified differentially expressed proteins, four up-regulated proteins (PLK1, CDK4, PLOD1 and PLOD2) associated with cell apoptosis, cell cycle and metastasis were chosen for the further investigation.
We show that PLOD2 is critical for fibrillar collagen formation by breast cancer cells, increases tumor stiffness, and is required for metastasis to lymph nodes and lungs.