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Date of Award
Various mechanical forces are present in the microenvironment of cancer cells which affect progression and metastasis of cancer. By employing an in vitro mechano-invasion assay, we found that mechanical stimulation leads to the maturation of invadopodia in human fibrosarcoma cells enhancing cell invasion. Invadopodia are F-actin rich protrusions that secrete proteolytic enzymes to promote the invasiveness of metastatic cancer cells and other naturally invasive cells. In this study we found that mechanical stimulation caused decreased expression and activity of PAK1 in human fibrosarcoma cells. Additionally, a constitutively active phosphorylation mutant of PAK1 disrupts the maturation of the invadopodium, while overexpression of a phosphorylation dead mutant enhances invadopodium maturation. Furthermore, we determined that mechanical stimulation could be responsible for the downregulation of MTSS1 causing it to be hypomethylated thereby decreasing its activity as a metastatic suppressor and promoting invasion.
Das, Anindita, "Pak1 And Mtss1 In The Mechanical Response Used In Cancer Invasion" (2022). Wayne State University Theses. 857.