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Over the last decades, some members of the protein tyrosine phosphatase family have emerged as cancer promoters. Among them, the Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) has been described to be associated with colorectal cancer liver metastasis and poor prostate cancer prognosis. Of importance in the process of cancer progression and metastasis is the interaction between tumor cells and platelets, as the latter are thought to promote several tumor hallmarks. Here, we examine to what extent LMWPTP expression in tumor cells affects their interaction with platelets. We demonstrate that the gene encoding LMWPTP is overexpressed in upper gastrointestinal (GI) cancer cell as well as colorectal cancer, and subsequently employ cell line models to show that the level of this phosphatase may be further augmented in the presence of platelets. We demonstrate that tumor-platelet interaction promotes GI tumor cell proliferation. Additionally, using know-down/-out models we show that LMWPTP expression in cancer cells contributes to a more efficient interaction with platelets and drives platelet-induced proliferation. These data are the first to demonstrate that phosphatases play a positive role in the tumor-promoting activities of platelets, with LMWPTP emerging as a key player promoting oncogenic phenotypic changes in tumor cells., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

In the past decade, significant progress has been made in understanding the role of protein tyrosine phosphatase as a positive regulator of tumor progression. In this scenario, our group was one of the first to report the involvement of the low molecular weight protein tyrosine phosphatase (LMWPTP or ACP1) in the process of resistance and migration of tumor cells. Later, we and others demonstrated a positive correlation between the amount of this enzyme in human tumors and the poor prognosis. With this information in mind, we asked if LMWPTP contribution to metastasis, would it have an action beyond the primary tumor site. We know that the amount of this enzyme in the tumor cell correlates positively with the ability of cancer cells to interact with platelets, an indication that this enzyme is also important for the survival of these cells in the bloodstream. Here, we discuss several molecular aspects that support the idea of LMWPTP as a signaling hub of cancer hallmarks. Chemical and genetic modulation of LMWPTP proved to shut down signaling pathways associated with cancer aggressiveness. Therefore, advances in the development of LMWPTP inhibitors have great applicability in human diseases such as cancer.

In the last decade, several reports highlight the importance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in cancer aggressiveness and resistance. Specifically, in chronic myeloid leukemia, we have reported that high expression of the LMWPTP maintains Src and Bcr-Abl kinases in an activated status and the glucose metabolism is directed to lactate production and, in turn, favor the pentoses pathway (one of the key process for antioxidant and protective responses). In this present study, we investigated the possible correlation between the LMWPTP and autophagy. In resistant chronic myeloid leukemia cells, the antioxidant response is supported by the glycolytic metabolism and antioxidant enzymes such as SOD and catalase, both favored by the LMWPTP. Therefore, when the cells were challenged by hydrogen peroxide treatment, the LMWPTP level goes down as well as SOD, and in turn, autophagy process was stimulated. The findings presented here reveal a novel aspect by which LMWPTP cooperates for the resistance of CML towards stressor stimuli.