Given the integral role of cancer associated fibroblasts in the production of a desmoplastic TME, and the aberrant remodeling of ECM proteins such as collagen-I and fibronectin, our observations that collagen triggers the phosphorylation of Annexin A2 provides potential explanation for the specific upregulation of phospho-Annexin A2 at Tyr 24 on tumor cells and within the TME seen in the study by Shen et al. Here, ANXA2 is linked to cancer.