AUTHOR=Hill Charlotte Nicole , Hernández-Cáceres Maria Paz , Asencio Catalina , Torres Begoña , Solis Benjamin , Owen Gareth I. TITLE=Deciphering the Role of the Coagulation Cascade and Autophagy in Cancer-Related Thrombosis and Metastasis JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.605314 DOI=10.3389/fonc.2020.605314 ISSN=2234-943X ABSTRACT=

Thrombotic complications are the second leading cause of death among oncology patients worldwide. Enhanced thrombogenesis has multiple origins and may result from a deregulation of megakaryocyte platelet production in the bone marrow, the synthesis of coagulation factors in the liver, and coagulation factor signaling upon cancer and the tumor microenvironment (TME). While a hypercoagulable state has been attributed to factors such as thrombocytosis, enhanced platelet aggregation and Tissue Factor (TF) expression on cancer cells, further reports have suggested that coagulation factors can enhance metastasis through increased endothelial-cancer cell adhesion and enhanced endothelial cell activation. Autophagy is highly associated with cancer survival as a double-edged sword, as can both inhibit and promote cancer progression. In this review, we shall dissect the crosstalk between the coagulation cascade and autophagic pathway and its possible role in metastasis and cancer-associated thrombosis formation. The signaling of the coagulation cascade through the autophagic pathway within the hematopoietic stem cells, the endothelial cell and the cancer cell are discussed. Relevant to the coagulation cascade, we also examine the role of autophagy-related pathways in cancer treatment. In this review, we aim to bring to light possible new areas of cancer investigation and elucidate strategies for future therapeutic intervention.