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Rac1-dependent lamellipodial motility in prostate cancer PC-3 cells revealed by optogenetic control of Rac1 activity Kato, Takuma 加藤, 琢磨 カトウ, タクマ 香川大学 Kagawa University 博士（医学） Abstract The lamellipodium, an essential structure for cell migration, plays an important role in the invasion and metastasis of cancer cells. Although Rac1 recognized as a key player in the formation of lamellipodia, the molecular mechanisms underlying lamellipodial motility are not fully understood. Optogenetic technology enabled us to spatiotemporally control the activity of photoactivatable Rac1 (PA-Rac1) in living cells. Using this system, we revealed the role of phosphatidylinositol 3-kinase (PI3K) in Rac1-dependent lamellipodial motility in PC-3 prostate cancer cells. Through local blue laser irradiation of PA-Rac1-expressing cells, lamellipodial motility was reversibly induced. First, outward extension of a lamellipodium parallel to the substratum was observed. The extended lamellipodium then showed ruffling activity at the periphery. Notably, PI(3,4,5)P3 and WAVE2 were localized in the extending lamellipodium in a PI3K-dependent manner. We confirmed that the inhibition of PI3K activity greatly suppressed lamellipodial extension, while the ruffling activity was less affected. These results suggest that Rac1-induced lamellipodial motility consists of two distinct activities, PI3K-dependent outward extension and PI3K-independent ruffling. doctoral thesis 2014-12-24 P application/pdf application/pdf application/pdf 甲第598号 https://kagawa-u.repo.nii.ac.jp/record/230/files/Med_A598.pdf https://kagawa-u.repo.nii.ac.jp/record/230/files/Med_A598_abstract.pdf https://kagawa-u.repo.nii.ac.jp/record/230/files/Med_A598_result.pdf https://kagawa-u.repo.nii.ac.jp/records/230 eng https://doi.org/10.1371/journal.pone.0097749 https://dl.ndl.go.jp/pid/10224393 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4029798/ 24848679 500000993871 Copyright: © 2014 Kato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. open access