Pyruvate analog acts as anti-metastatic agent by targeting LMWPTP on colorectal cancer

The effectiveness of the therapy of several tumors is still a challenge, especially in metastatic cases. Our group has explored signal transduction pathways for identifying targets to overcome tumor aggressiveness. We have identified the low molecular weight protein phosphatase (LMWPTP) as a relevant player in cancer migration and resistance to drugs. Recently, we reported that the platelet aggregation correlates with the metastatic potential of cancer (Faria et al, 2019) as part of hematogenous dissemination of cancer. Therefore, in the present study we aimed to investigate whether this phosphatase would also act in cancer microenvironment by tracking platelet responsiveness and epithelial-mesenchymal transition markers after exposing CRC cells to 3-bromopyruvate (3-BP). 3-BP inhibits the LMWPTP which decreases the platelet responsiveness efficiency to collagen and thrombin. In addition, this pyruvate analog disrupts CRC epithelial-mesenchymal transition potential. In summary, 3BP appears as a candidate for preventing tumor metastasis by targeting invasion and hematogenous dissemination.