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Environmentally dependent and independent control of 3D cell shape.
- Source :
-
Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114016. Date of Electronic Publication: 2024 Apr 17. - Publication Year :
- 2024
-
Abstract
- How cancer cells determine their shape in response to three-dimensional (3D) geometric and mechanical cues is unclear. We develop an approach to quantify the 3D cell shape of over 60,000 melanoma cells in collagen hydrogels using high-throughput stage-scanning oblique plane microscopy (ssOPM). We identify stereotypic and environmentally dependent changes in shape and protrusivity depending on whether a cell is proximal to a flat and rigid surface or is embedded in a soft environment. Environmental sensitivity metrics calculated for small molecules and gene knockdowns identify interactions between the environment and cellular factors that are important for morphogenesis. We show that the Rho guanine nucleotide exchange factor (RhoGEF) TIAM2 contributes to shape determination in environmentally independent ways but that non-muscle myosin II, microtubules, and the RhoGEF FARP1 regulate shape in ways dependent on the microenvironment. Thus, changes in cancer cell shape in response to 3D geometric and mechanical cues are modulated in both an environmentally dependent and independent fashion.<br />Competing Interests: Declaration of interests C.D. has a licensed granted patent on the optical arrangement for oblique plane microscopy (OPM) under patent nos. US 8582203 B2 and EP 2316048 B1.<br /> (Copyright © 2024. Published by Elsevier Inc.)
- Subjects :
- Humans
Cell Line, Tumor
Microtubules metabolism
Myosin Type II metabolism
Rho Guanine Nucleotide Exchange Factors metabolism
Rho Guanine Nucleotide Exchange Factors genetics
Melanoma pathology
Melanoma metabolism
Guanine Nucleotide Exchange Factors metabolism
Guanine Nucleotide Exchange Factors genetics
Cell Shape
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 38636520
- Full Text :
- https://doi.org/10.1016/j.celrep.2024.114016