Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells

Ajai J. Pulianmackal; Dan Sun; Kenji Yumoto; Zhengda Li; Yu Chih Chen; Meha V. Patel; Yu Wang; Euisik Yoon; Alexander Pearson; Qiong Yang; Russell Taichman; Frank C. Cackowski; Laura A. Buttitta

doi:10.3389/fcell.2021.728663

Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells

Ajai J. Pulianmackal, Dan Sun, Kenji Yumoto, Zhengda Li, Yu Chih Chen, Meha V. Patel, Yu Wang, Euisik Yoon, Alexander Pearson, Qiong Yang, Russell Taichman, Frank C. Cackowski, Laura A. Buttitta

Yonsei Advanced Science Institute

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

The proliferation-quiescence decision is a dynamic process that remains incompletely understood. Live-cell imaging with fluorescent cell cycle sensors now allows us to visualize the dynamics of cell cycle transitions and has revealed that proliferation-quiescence decisions can be highly heterogeneous, even among clonal cell lines in culture. Under normal culture conditions, cells often spontaneously enter non-cycling G0 states of varying duration and depth. This also occurs in cancer cells and G0 entry in tumors may underlie tumor dormancy and issues with cancer recurrence. Here we show that a cell cycle indicator previously shown to indicate G0 upon serum starvation, mVenus-p27K-, can also be used to monitor spontaneous quiescence in untransformed and cancer cell lines. We find that the duration of spontaneous quiescence in untransformed and cancer cells is heterogeneous and that a portion of this heterogeneity results from asynchronous proliferation-quiescence decisions in pairs of daughters after mitosis, where one daughter cell enters or remains in temporary quiescence while the other does not. We find that cancer dormancy signals influence both entry into quiescence and asynchronous proliferation-quiescence decisions after mitosis. Finally, we show that spontaneously quiescent prostate cancer cells exhibit altered expression of components of the Hippo pathway and are enriched for the stem cell markers CD133 and CD44. This suggests a hypothesis that dormancy signals could promote cancer recurrence by increasing the proportion of quiescent tumor cells poised for cell cycle re-entry with stem cell characteristics in cancer.

Original language	English
Article number	728663
Journal	Frontiers in Cell and Developmental Biology
Volume	9
DOIs	https://doi.org/10.3389/fcell.2021.728663
Publication status	Published - 2021 Dec 10

Bibliographical note

Funding Information:
This work in the Buttitta Lab was supported by funding from the American Cancer Society (RSG-15–161–01-DDC), and the Dept. of Defense (W81XWH1510413). Work in the Yang Lab is supported by the National Science Foundation (Early CAREER Grant #1553031 and MCB#1817909) and the National Institutes of Health (MIRA GM119688). Work in the Pearson lab is supported by the National Institutes of Health (K08-DE026500 and U01-CA243075). Work in the Yoon Lab was in part supported by the National Institute of Health (R01-CA203810). Work in the Cackowski Lab is supported by a Prostate Cancer Foundation Challenge award, University of Michigan Prostate Cancer S.P.O.R.E. NIH/NCI 5 P50CA18678605, Career Enhancement sub-award to F.C.C. F048931, Prostate Cancer Foundation Young Investigator Award 18YOUN04, Department of Defense Prostate Cancer Research Program Physician Research Award W81XWH2010394, and start-up funds from The University of Michigan and Karmanos Cancer Institute. Work in the Taichman lab was supported by National Institutes of Health (3P01CA093900-06) and the Prostate Cancer Foundation (16CHAL05).

Funding Information:
This work in the Buttitta Lab was supported by funding from the American Cancer Society (RSG-15–161–01-DDC), and the Dept. of Defense (W81XWH1510413). Work in the Yang Lab is supported by the National Science Foundation (Early CAREER Grant #1553031 and MCB#1817909) and the National Institutes of Health (MIRA GM119688). Work in the Pearson lab is supported by the National Institutes of Health (K08-DE026500

Publisher Copyright:
Copyright © 2021 Pulianmackal, Sun, Yumoto, Li, Chen, Patel, Wang, Yoon, Pearson, Yang, Taichman, Cackowski and Buttitta.

All Science Journal Classification (ASJC) codes

Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fcell.2021.728663

Cite this

Pulianmackal, A. J., Sun, D., Yumoto, K., Li, Z., Chen, Y. C., Patel, M. V., Wang, Y., Yoon, E., Pearson, A., Yang, Q., Taichman, R., Cackowski, F. C., & Buttitta, L. A. (2021). Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells. Frontiers in Cell and Developmental Biology, 9, [728663]. https://doi.org/10.3389/fcell.2021.728663

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title = "Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells",

abstract = "The proliferation-quiescence decision is a dynamic process that remains incompletely understood. Live-cell imaging with fluorescent cell cycle sensors now allows us to visualize the dynamics of cell cycle transitions and has revealed that proliferation-quiescence decisions can be highly heterogeneous, even among clonal cell lines in culture. Under normal culture conditions, cells often spontaneously enter non-cycling G0 states of varying duration and depth. This also occurs in cancer cells and G0 entry in tumors may underlie tumor dormancy and issues with cancer recurrence. Here we show that a cell cycle indicator previously shown to indicate G0 upon serum starvation, mVenus-p27K-, can also be used to monitor spontaneous quiescence in untransformed and cancer cell lines. We find that the duration of spontaneous quiescence in untransformed and cancer cells is heterogeneous and that a portion of this heterogeneity results from asynchronous proliferation-quiescence decisions in pairs of daughters after mitosis, where one daughter cell enters or remains in temporary quiescence while the other does not. We find that cancer dormancy signals influence both entry into quiescence and asynchronous proliferation-quiescence decisions after mitosis. Finally, we show that spontaneously quiescent prostate cancer cells exhibit altered expression of components of the Hippo pathway and are enriched for the stem cell markers CD133 and CD44. This suggests a hypothesis that dormancy signals could promote cancer recurrence by increasing the proportion of quiescent tumor cells poised for cell cycle re-entry with stem cell characteristics in cancer.",

author = "Pulianmackal, {Ajai J.} and Dan Sun and Kenji Yumoto and Zhengda Li and Chen, {Yu Chih} and Patel, {Meha V.} and Yu Wang and Euisik Yoon and Alexander Pearson and Qiong Yang and Russell Taichman and Cackowski, {Frank C.} and Buttitta, {Laura A.}",

note = "Funding Information: This work in the Buttitta Lab was supported by funding from the American Cancer Society (RSG-15–161–01-DDC), and the Dept. of Defense (W81XWH1510413). Work in the Yang Lab is supported by the National Science Foundation (Early CAREER Grant #1553031 and MCB#1817909) and the National Institutes of Health (MIRA GM119688). Work in the Pearson lab is supported by the National Institutes of Health (K08-DE026500 and U01-CA243075). Work in the Yoon Lab was in part supported by the National Institute of Health (R01-CA203810). Work in the Cackowski Lab is supported by a Prostate Cancer Foundation Challenge award, University of Michigan Prostate Cancer S.P.O.R.E. NIH/NCI 5 P50CA18678605, Career Enhancement sub-award to F.C.C. F048931, Prostate Cancer Foundation Young Investigator Award 18YOUN04, Department of Defense Prostate Cancer Research Program Physician Research Award W81XWH2010394, and start-up funds from The University of Michigan and Karmanos Cancer Institute. Work in the Taichman lab was supported by National Institutes of Health (3P01CA093900-06) and the Prostate Cancer Foundation (16CHAL05). Funding Information: This work in the Buttitta Lab was supported by funding from the American Cancer Society (RSG-15–161–01-DDC), and the Dept. of Defense (W81XWH1510413). Work in the Yang Lab is supported by the National Science Foundation (Early CAREER Grant #1553031 and MCB#1817909) and the National Institutes of Health (MIRA GM119688). Work in the Pearson lab is supported by the National Institutes of Health (K08-DE026500 Publisher Copyright: Copyright {\textcopyright} 2021 Pulianmackal, Sun, Yumoto, Li, Chen, Patel, Wang, Yoon, Pearson, Yang, Taichman, Cackowski and Buttitta.",

year = "2021",

month = dec,

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doi = "10.3389/fcell.2021.728663",

language = "English",

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AU - Pulianmackal, Ajai J.

AU - Sun, Dan

AU - Yumoto, Kenji

AU - Li, Zhengda

AU - Chen, Yu Chih

AU - Patel, Meha V.

AU - Wang, Yu

AU - Yoon, Euisik

AU - Pearson, Alexander

AU - Yang, Qiong

AU - Taichman, Russell

AU - Cackowski, Frank C.

AU - Buttitta, Laura A.

N1 - Funding Information: This work in the Buttitta Lab was supported by funding from the American Cancer Society (RSG-15–161–01-DDC), and the Dept. of Defense (W81XWH1510413). Work in the Yang Lab is supported by the National Science Foundation (Early CAREER Grant #1553031 and MCB#1817909) and the National Institutes of Health (MIRA GM119688). Work in the Pearson lab is supported by the National Institutes of Health (K08-DE026500 and U01-CA243075). Work in the Yoon Lab was in part supported by the National Institute of Health (R01-CA203810). Work in the Cackowski Lab is supported by a Prostate Cancer Foundation Challenge award, University of Michigan Prostate Cancer S.P.O.R.E. NIH/NCI 5 P50CA18678605, Career Enhancement sub-award to F.C.C. F048931, Prostate Cancer Foundation Young Investigator Award 18YOUN04, Department of Defense Prostate Cancer Research Program Physician Research Award W81XWH2010394, and start-up funds from The University of Michigan and Karmanos Cancer Institute. Work in the Taichman lab was supported by National Institutes of Health (3P01CA093900-06) and the Prostate Cancer Foundation (16CHAL05). Funding Information: This work in the Buttitta Lab was supported by funding from the American Cancer Society (RSG-15–161–01-DDC), and the Dept. of Defense (W81XWH1510413). Work in the Yang Lab is supported by the National Science Foundation (Early CAREER Grant #1553031 and MCB#1817909) and the National Institutes of Health (MIRA GM119688). Work in the Pearson lab is supported by the National Institutes of Health (K08-DE026500 Publisher Copyright: Copyright © 2021 Pulianmackal, Sun, Yumoto, Li, Chen, Patel, Wang, Yoon, Pearson, Yang, Taichman, Cackowski and Buttitta.

PY - 2021/12/10

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N2 - The proliferation-quiescence decision is a dynamic process that remains incompletely understood. Live-cell imaging with fluorescent cell cycle sensors now allows us to visualize the dynamics of cell cycle transitions and has revealed that proliferation-quiescence decisions can be highly heterogeneous, even among clonal cell lines in culture. Under normal culture conditions, cells often spontaneously enter non-cycling G0 states of varying duration and depth. This also occurs in cancer cells and G0 entry in tumors may underlie tumor dormancy and issues with cancer recurrence. Here we show that a cell cycle indicator previously shown to indicate G0 upon serum starvation, mVenus-p27K-, can also be used to monitor spontaneous quiescence in untransformed and cancer cell lines. We find that the duration of spontaneous quiescence in untransformed and cancer cells is heterogeneous and that a portion of this heterogeneity results from asynchronous proliferation-quiescence decisions in pairs of daughters after mitosis, where one daughter cell enters or remains in temporary quiescence while the other does not. We find that cancer dormancy signals influence both entry into quiescence and asynchronous proliferation-quiescence decisions after mitosis. Finally, we show that spontaneously quiescent prostate cancer cells exhibit altered expression of components of the Hippo pathway and are enriched for the stem cell markers CD133 and CD44. This suggests a hypothesis that dormancy signals could promote cancer recurrence by increasing the proportion of quiescent tumor cells poised for cell cycle re-entry with stem cell characteristics in cancer.

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Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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