Figure 9.

Proposed OSF-2 function in promoting (lymph node) metastases by regulating the tumor microenvironment and cellular survival. OSF-2 is overexpressed in tumor cells, as well as in cancer-associated fibroblasts (CAFs) at the primary tumor and lymph node metastatic sites in HNC. Though, it is likely that these mechanisms are also relevant for distant site metastases in other cancer types. Due to the conserved N-terminal secretion signal, OSF-2 seems to execute its tumor-promoting functions not mainly intracellularly, but extracellularly in the tumor microenvironment. Here, secretion inhibitors could be therapeutically relevant. OSF-2 modulates the tumor microenvironment by integrin-dependent activation of Akt/PKB pathways and downstream signaling, particularly critical under stress conditions.