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Real‐time cell cycle imaging during melanoma growth, invasion, and drug response
Author(s) -
Haass Nikolas K.,
Beaumont Kimberley A.,
Hill David S.,
Anfosso Andrea,
Mrass Paulus,
Munoz Marcia A.,
Kinjyo Ichiko,
Weninger Wolfgang
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12274
Subject(s) - melanoma , cell cycle , cell growth , microbiology and biotechnology , motility , cancer research , cell , biology , in vivo , cell cycle progression , biochemistry , genetics
Summary Solid cancers are composed of heterogeneous zones containing proliferating and quiescent cells. Despite considerable insight into the molecular mechanisms underlying aberrant cell cycle progression, there is limited understanding of the relationship between the cell cycle on the one side, and melanoma cell motility, invasion, and drug sensitivity on the other side. Utilizing the fluorescent ubiquitination‐based cell cycle indicator ( FUCCI ) to longitudinally monitor proliferation and migration of melanoma cells in 3D culture and in vivo , we found that invading melanoma cells cycle actively, while G1‐arrested cells showed decreased invasion. Melanoma cells in a hypoxic environment or treated with mitogen‐activated protein kinase pathway inhibitors remained G1‐arrested for extended periods of time, with proliferation and invasion resuming after re‐exposure to a more favorable environment. We challenge the idea that the invasive and proliferative capacity of melanoma cells are mutually exclusive and further demonstrate that a reversibly G1‐arrested subpopulation survives in the presence of targeted therapies.