Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity

Molecular Cancer
Rodney B LuworHong-Jian Zhu

Abstract

Metastasis is a process where only a small subset of cells is capable of successfully migrating to and propagating at secondary sites. TGF-β signalling is widely known for its role in cancer metastasis and is associated with cell migration in whole cell populations. We extend these findings by investigating the role of TGF-β signalling in promoting migration and motility by imaging the signalling activity in live, individual MDA-MB-231 cancer cells utilizing a novel Smad3 Td-Tomato reporter adenovirus. Here we find that not all MDA-MB-231 cancer cells have similar TGF-β mediated Smad3 transcription activity and display at least two distinct migratory populations. Importantly, Smad3 activity was significantly higher within migratory cells compared to non-migrated cells in wound healing and transwell assays. Furthermore, time-lapse experiments showed that MDA-MB-231 cells displaying Smad3 activity moved faster and a greater distance compared to cells not displaying Smad3 reporter activity. Interestingly, despite being more motile than cells with undetectable levels of Smad3 activity, high Smad3 activity was detrimental to cell motility compared to low and medium level of Smad3 activity. We have developed a method enabling real-ti...Continue Reading

References

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Citations

Dec 19, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Guodong LiFeng Gao
Apr 11, 2019·PLoS Computational Biology·Julien VarennesBumsoo Han
Jan 15, 2017·Journal of Molecular Endocrinology·Tram B DoanChristine L Clarke
Aug 1, 2020·Frontiers in Cell and Developmental Biology·Adilson Fonseca TeixeiraHong-Jian Zhu

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Methods Mentioned

BETA
confocal microscopy
PCR
Destination
transfection
Assay

Software Mentioned

image J
Metamorph
imageJ

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