Project Advisor(s) (Students Only)
Dr. Scott Gehler
Presentation Type (All Applicants)
Poster Presentation
Disciplines (All Applicants)
Biology | Cancer Biology | Cell Biology
Description, Abstract, or Artist's Statement
Cell migration is essential for many life processes, including wound healing, embryonic development and cancer metastasis. Cells move across a surface by interacting and forming adhesions with the molecules in their environment, specifically the extracellular matrix. Past studies have shown that there is an optimal level of cell-substratum adhesive strength that allows for the most cell migration and spreading (DiMilla et al., 1993; Gaudet et al., 2003). The mechanism by which this works is not well understood, however. Semaphorin 3A (Sema3A) has been shown to increase the expression of integrin receptors, which help mediate the formation of the adhesions between a cell and its substrate in breast cancer cells, but also inhibit the motility of these cells (Pan et al. 2009). We propose that Sema3A changes cell adhesion dynamics to cause the change in breast cancer cell migration on different concentrations of various ECM. First, MDA-MB-231 breast epithelial cell migration and spreading were measured on various concentrations of collagen type 1, fibronectin and laminin 1. The results demonstrate that Sema3A inhibits cell migration and spreading on high concentrations of collagen but enhances cell migration and spreading at lower collagen concentrations. In addition, analysis of cell morphology demonstrates that Sema3A-treated cells were more elongated on all concentrations of collagen. Sema3A had less robust effects on cell migration, spreading and morphology when cultured on fibronectin and laminin. Second, inhibition of Rho-associated protein kinase (ROCK) blocks the Sema3A-mediated effects on cell migration and spreading when cultured on all concentrations of collagen. Third, Sema3A increases focal adhesion formation on all concentrations of collagen and fibronectin, but not laminin. However, inhibition of ROCK blocks Sema3A-enhanced focal adhesion formation on collagen. These results suggest that Sema3A shifts the optimal level of cell-matrix adhesions to a non-optional ECM concentration—in particular collagen, to yield maximal cell migration and spreading that is mediated through a ROCK-dependent mechanism.
Augustana Digital Commons Citation
Compere, Frances V. and Gehler, Scott. "Semaphorin3A Increases Focal Adhesion Formation to Shift the Relationship Between Cell Migration and Substratum Concentration Through a ROCK-dependent Mechanism" (2016). Celebration of Learning.
https://digitalcommons.augustana.edu/celebrationoflearning/2016/posters/10
Semaphorin3A Increases Focal Adhesion Formation to Shift the Relationship Between Cell Migration and Substratum Concentration Through a ROCK-dependent Mechanism
Cell migration is essential for many life processes, including wound healing, embryonic development and cancer metastasis. Cells move across a surface by interacting and forming adhesions with the molecules in their environment, specifically the extracellular matrix. Past studies have shown that there is an optimal level of cell-substratum adhesive strength that allows for the most cell migration and spreading (DiMilla et al., 1993; Gaudet et al., 2003). The mechanism by which this works is not well understood, however. Semaphorin 3A (Sema3A) has been shown to increase the expression of integrin receptors, which help mediate the formation of the adhesions between a cell and its substrate in breast cancer cells, but also inhibit the motility of these cells (Pan et al. 2009). We propose that Sema3A changes cell adhesion dynamics to cause the change in breast cancer cell migration on different concentrations of various ECM. First, MDA-MB-231 breast epithelial cell migration and spreading were measured on various concentrations of collagen type 1, fibronectin and laminin 1. The results demonstrate that Sema3A inhibits cell migration and spreading on high concentrations of collagen but enhances cell migration and spreading at lower collagen concentrations. In addition, analysis of cell morphology demonstrates that Sema3A-treated cells were more elongated on all concentrations of collagen. Sema3A had less robust effects on cell migration, spreading and morphology when cultured on fibronectin and laminin. Second, inhibition of Rho-associated protein kinase (ROCK) blocks the Sema3A-mediated effects on cell migration and spreading when cultured on all concentrations of collagen. Third, Sema3A increases focal adhesion formation on all concentrations of collagen and fibronectin, but not laminin. However, inhibition of ROCK blocks Sema3A-enhanced focal adhesion formation on collagen. These results suggest that Sema3A shifts the optimal level of cell-matrix adhesions to a non-optional ECM concentration—in particular collagen, to yield maximal cell migration and spreading that is mediated through a ROCK-dependent mechanism.