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dc.contributor.authorPratt, S.J.P.
dc.contributor.authorLee, R.M.
dc.contributor.authorHernández-Ochoa, E.O.en_US
dc.date.accessioned2019-06-21T18:46:27Z
dc.date.available2019-06-21T18:46:27Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85047216878&doi=10.18632%2foncotarget.25186&partnerID=40&md5=e39ea9f15fe1d95824f2fd18bb670bea
dc.identifier.urihttp://hdl.handle.net/10713/9703
dc.description.abstractAggressive cellular phenotypes such as uncontrolled proliferation and increased migration capacity engender cellular transformation, malignancy and metastasis. While genetic mutations are undisputed drivers of cancer initiation and progression, it is increasingly accepted that external factors are also playing a major role. Two recently studied modulators of breast cancer are changes in the cellular mechanical microenvironment and alterations in calcium homeostasis. While many studies investigate these factors separately in breast cancer cells, very few do so in combination. This current work sets a foundation to explore mechano-calcium relationships driving malignant progression in breast cancer. Utilizing real-time imaging of an in vitro scratch assay, we were able to resolve mechanically-sensitive calcium signaling in human breast cancer cells. We observed rapid initiation of intracellular calcium elevations within seconds in cells at the immediate wound edge, followed by a time-dependent increase in calcium in cells at distances up to 500μm from the scratch wound. Calcium signaling to neighboring cells away from the wound edge returned to baseline within seconds. Calcium elevations at the wound edge however, persisted for up to 50 minutes. Rigorous quantification showed that extracellular calcium was necessary for persistent calcium elevation at the wound edge, but intercellular signal propagation was dependent on internal calcium stores. In addition, intercellular signaling required extracellular ATP and activation of P2Y 2 receptors. Through comparison of scratch-induced signaling from multiple cell lines, we report drastic reductions in response from aggressively tumorigenic and metastatic cells. The real-time scratch assay established here provides quantitative data on the molecular mechanisms that support rapid scratch-induced calcium signaling in breast cancer cells. These mechanisms now provide a clear framework for investigating which short-term calcium signals promote long-term changes in cancer cell biology. Copyright Pratt et al.en_US
dc.description.sponsorshipThis work was supported by the Kahlert Foundation and grants from the National Institutes of Health to SSM (R01-CA124704, R01-CA154624), SJPP (5T32GM008181-30), RML (T32CA154274), MIV (K01CA166576), MFS (R37-AR055099).en_US
dc.description.urihttps://dx.doi.org/10.18632/oncotarget.25186en_US
dc.language.isoen-USen_US
dc.publisherImpact Journals LLCen_US
dc.relation.ispartofOncotarget
dc.subjectCalciumen_US
dc.subjectHuman breast canceren_US
dc.subjectIntercellular signalingen_US
dc.subjectMechanotransductionen_US
dc.subjectPurinergic receptoren_US
dc.titleReal-time scratch assay reveals mechanisms of early calcium signaling in breast cancer cells in response to woundingen_US
dc.typeArticleen_US
dc.identifier.doi10.18632/oncotarget.25186


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