Abstract
Breast cancer remains one of the leading causes of cancer-related mortality worldwide among adults. Metastasis, the ability for cancer cells to translocate from its primary tissue to distinct tissues, is one of the key factors leading to its high fatal rate. Therefore, efforts had been made on understanding mechanisms of metastasis by studying bio-molecules, cytoskeletal architecture and the behavior of highly aggressive cancer cells lines. Among them, actin and myosin protein families, have garnered considerable attention due to their critical role in cytoskeletal dynamics during migration. Cellular structure formed by actin like filopodia which locate on the leading edge of cell as finger-like protrusion was reported to correlate with metastasis speed by promoting extracellular matrix degradation. Also, evidences suggest Myosin 10 (Myo10), an unconventional myosin on tip of filopodia, initiate its formation and highly correlate promoting cancer cells metastasis. Despite the phenomenological significance from previous work, the mechanical reasons of increased metastasis ability remain illusive. In this thesis, I performed knock-down of Myo10 in MBD-MB-231, an aggressive triple-negative breast cancer cell line, to decrease the expression level of Myo10 in these cells. This allow me to compare the traction force exerted by the cancer cells to surrounding during migration using Traction Force Microscopy (TFM) between the knock-down group (KD) and the control. By analyzing and comparing the spatial-temporal data obtained from the KD and control groups, I found the strain energy and traction moment of the breast cancer cells were decreased significantly in the KD group compare to the control, implying that Myo10 important role in generation of traction force. Besides, the analysis on the alignment of the morphological and traction force major axis shows the cosine similarity between them remain similar amoung the KD and control. This results shows that Myo10 alter play less significant role in dictating directional migration. To sum up, my results indicate Myo10 is important in overall migration ability in terms of the strain energy and effective traction force of the breast cancer cells.