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Clustered localization of STAT3 during the cell cycle detected by super-resolution fluorescence microscopy
Jing Gao1, Junling Chen1, Mingjun Cai1
1State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People's Republic of China.
Abstract:
Signal transducer and activator of transcription 3 (STAT3) plays a key role in various cellular processes such as cell proliferation, differentiation, apoptosis and immune responses. In particular, STAT3 has emerged as a potential molecular target for cancer therapy. The functional role and standard activation mechanism of STAT3 have been well studied, however, the spatial distribution of STAT3 during the cell cycle is poorly known. Therefore, it is indispensable to study STAT3 spatial arrangement and nuclear-cytoplasimic localization at the different phase of cell cycle in cancer cells. By direct stochastic optical reconstruction microscopy imaging, we find that STAT3 forms various number and size of clusters at the different cell-cycle stage, which could not be clearly observed by conventional fluorescent microscopy. STAT3 clusters get more and larger gradually from G1 to G2 phase, during which time transcription and other related activities goes on consistently. The results suggest that there is an intimate relationship between the clustered characteristic of STAT3 and the cell-cycle behavior. Meanwhile, clustering would facilitate STAT3 rapid response to activating signals due to short distances between molecules. Our data might open a new door to develop an antitumor drug for inhibiting STAT3 signaling pathway by destroying its clusters.
Insights
Signal transducer and activator of transcription 3 (STAT3) forms clusters that grow during the cell cycle. This clustering may enhance STAT3
Area of Science:
- Cellular Biology
- Molecular Biology
- Cancer Research
Background:
- Signal transducer and activator of transcription 3 (STAT3) is crucial for cell functions and a cancer therapy target.
- STAT3's role in cell cycle progression and its spatial distribution are not well understood.
Purpose of the Study:
- Investigate STAT3's spatial arrangement and localization during the cell cycle in cancer cells.
- Characterize STAT3 clustering dynamics throughout different cell cycle phases.
Main Methods:
- Utilized direct stochastic optical reconstruction microscopy (dSTORM) for high-resolution imaging.
- Analyzed STAT3 cluster formation, number, and size at distinct cell cycle stages.
Main Results:
- STAT3 forms distinct clusters whose number and size vary with cell cycle stage.
- Clusters progressively increase in size and number from G1 to G2 phase.
- Observed STAT3 clustering dynamics not discernible with conventional microscopy.
Conclusions:
- STAT3 clustering is closely linked to cell cycle progression and behavior.
- Clustering may enable faster STAT3 signaling responses.
- Targeting STAT3 clusters presents a novel strategy for anti-cancer drug development.