Abstract
Ca2+ signaling plays an important role in cell migration and cancer metastasis, but how calcium coordinates other structural components to regulate cell migration machinery and cancer progression remains unclear. Searching for novel calcium regulatory molecules and discovering the interaction between calcium and these molecules may help us understand how calcium controls proper cell motility.
The microtubule and actin cross-linking factor 1 (MACF1), also called actin cross-linking factor 7 (ACF7), bridges microtubule and actin to shape the morphology of cells and sustain directional cell movement. The existence of calcium binding EF-hand motif in MACF1 suggests that Ca2+ regulates MACF1 to control cell migration.
We therefore study how Ca2+ interacts with MACF1 to regulate cell migration and cancer metastasis. To validate the effect of MACF1 on cell migration, we suppressed and overexpressed MACF1 in SAS, a head and neck squamous cell carcinoma cell line, and conducted scratch wound healing assays. Surprisingly, knocking down MACF1 in SAS improved coordination, persistence, and polarity during migration. We further investigated how MACF1 manipulated cell migration machinery, by inhibiting both MACF1 and one of the actin-modulating molecules- alpha-catenin, Rac1, paxillin and myosin-light chain kinase. We found that knocking down CTNNA1 to destroy cell-cell coordination eliminated the effect of shMACF1, suggesting the importance of cell-cell interactions on MACF1-mediated cell migration. We are currently working on their molecular mechanisms and proceeding to explore the characteristics and significance of Ca2+-MACF1 interactions, which will benefit new drug development.
