MICAL1 in Tumour Cell Motility

The triple-negative breast cancer (TNBC) subtype is the most difficult to treat and has a higher risk of metastasis. Cancer cell metastasis requires the involvement of the actin cytoskeleton. The molecule interacting with CasL protein 1 (MICAL1) is a monooxygenase enzyme that facilitates the local disassociation of actin monomers to promote actin filamentation. The epidermal growth factor receptor (EGFR) is a tyrosine kinase that promotes cell invasion, migration, growth, and survival. Metastatic characteristics are promoted in TNBC during aberrant EGFR signalling, via the mitogenactivated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt pathways. This thesis will examine how MICAL1 influences motility, morphology, and EGFR signalling in TNBC cell lines. Results from this thesis demonstrate that MICAL1 contributes to confined cell migration and cell size. Further, results demonstrate that MICAL1 negatively modulates MAPK signalling during EGF stimulation. In effect, this thesis forwards MICAL1 as a likely contributor of TNBC cell metastasis.