Figure 12. Working model summarizing the main findings described in this study identifying the mechanisms by which cytotoxic drugs induce CAV1 expression.

Initially, CAV1 expression is repressed by methylation in the gene promoter region in tumor cells. Exposure to the anti-neoplastic drugs Methotrexate or Etoposide induces promoter demethylation that increases transcription and expression of CAV1 that is is mediated by ERK activation and ROS production. Likewise, ROS are shown to promote Src family kinase-dependent CAV1 phosphorylation that may lead to Rac1 and metalloproteinase activation, as well as increased migration, invasion and metastasis.