Fig. 5: Proposed mechanism of copper depletion’s effects on collagen remodeling in the pre-metastatic niche.

In those without disease progression/death, TM-associated copper depletion may lead to decreased collagen cross-linking, as measured by LOXL2 levels, and increased collagen degradation over formation (C1M/Pro-C3), thereby “normalizing” the pre-metastatic niche ECM and preventing tumor metastasis.