Single-cell morphology encodes metastatic potential
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Cancer cell population exhibits great cellular heterogeneity, and single-cell morphology encodes metastatic potential.
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DNA content and cell cycle phases can be identified from intensity of fluorescently labeled nuclei in images.
“It has been shown in our previous studies that DNA content and cell cycle phases can be identified from the intensity of fluorescently labeled nuclei in images [24–26].”
From Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during senescence induction (2025) · cites this paper as [26]
The Materials and Methods section (Immunostaining and fluorescence microscopy; page unavailable) says the authors stained nuclear DNA with Hoechst 33342 and recorded fluorescence images. It does not say they used nuclear fluorescence intensity to determine DNA content or identify cell-cycle phases. The Results section (Distinct gene expression profiles of SCCs reveal prognostic genes; page unavailable) instead describes assessing ploidy by counting chromosomes in metaphase spreads. (LLM, conf=0.82)
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Cites
<i>EGFR</i> Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368 · see citing works
Jayatilaka, H., Tyle, P., Chen, J. J., Kwak, M., Ju, J., Kim, H. J., Lee, J. S. H., Wu, P.-H., Gilkes, D. M., Fan, R., et al. (2017) · Nature Communications · doi:10.1038/ncomms15584 · Cited by 177 · see citing works
Self-citationEvolution of cellular morpho-phenotypes in cancer metastasis.
Wu, P.-H., Phillip, J. M., Khatau, S. B., Chen, W.-C., Stirman, J., Rosseel, S., Tschudi, K., Van Patten, J., Wong, M., Gupta, S., et al. (2015) · Scientific Reports · doi:10.1038/srep18437 · Cited by 117 · see citing works
Self-citationChambliss, A. B., Wu, P., Chen, W., Sun, S. X., & Wirtz, D. (2013) · The FASEB Journal · doi:10.1096/fj.12-227108 · Cited by 34 · see citing works
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Research works printed but not linked: 41
- [1]Stratton M. R., Campbell P. J., Futreal P. A., The cancer genome. Nature 458, 719– 724 (2009). 19360079 PMC2821689
- [2]Vogelstein B., Papadopoulos N., Velculescu V. E., Zhou S., Diaz L. A., Kinzler K. W., Cancer genome landscapes. Science 339, 1546– 1558 (2013). 23539594 PMC3749880
- [4]Miki Y., Swensen J., Shattuck-Eidens D., Futreal P., Harshman K., Tavtigian S., Liu Q., Cochran C., Bennett L., Ding W., A strong candidate for the breast and ovarian-cancer susceptibility gene brca1. Science 266, 66– 71 (1994). 7545954
- [5]Negrini S., Gorgoulis V. G., Halazonetis T. D., Genomic instability - an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 11, 220– 228 (2010). 20177397
- [6]Potapova T. A., Zhu J., Li R., Aneuploidy and chromosomal instability: A vicious cycle driving cellular evolution and cancer genome chaos. Cancer Metast. Rev. 32, 377– 389 (2013). PMC3825812 23709119
- [7]Nguyen A., Yoshida M., Goodarzi H., Tavazoie S. F., Highly variable cancer subpopulations that exhibit enhanced transcriptome variability and metastatic fitness. Nat. Commun. 7, 11246 (2016). 27138336 PMC4857405
- [8]Minn A. J., Kang Y., Serganova I., Gupta G. P., Giri D. D., Doubrovin M., Ponomarev V., Gerald W. L., Blasberg R., Massagué J., Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J. Clin. Invest. 115, 44– 55 (2005). 15630443 PMC539194
- [9]Yin Z., Sadok A., Sailem H., McCarthy A., Xia X., Li F., Garcia M. A., Evans L., Barr A. R., Perrimon N., Marshall C. J., Wong S. T. C., Bakal C., A screen for morphological complexity identifies regulators of switch-like transitions between discrete cell shapes. Nat. Cell Biol. 15, 860– 871 (2013). 23748611 PMC3712499
- [10]Bakal C., Aach J., Church G., Perrimon N., Quantitative morphological signatures define local signaling networks regulating cell morphology. Science 316, 1753– 1756 (2007). 17588932
- [12]Ayyoub M., Scarlata C. M., Hamai A., Pignon P., Valmori D., Expression of MAGE-A3/6 in primary breast cancer is associated with hormone receptor negative status, high histologic grade, and poor survival. J. Immunother. 37, 73– 76 (2014). 24509169
- [13]Chen W. C., Wu P. H., Phillip J. M., Khatau S. B., Choi J. M., Dallas M. R., Konstantopoulos K., Sun S. X., Lee J. S. H., Hodzic D., Wirtz D., Functional interplay between the cell cycle and cell phenotypes. Integr. Biol. 5, 523– 534 (2013). PMC3813296 23319145
- [14]Wu P. H., Hung S. H., Ren T. N., Shih I. M., Tseng Y., Cell cycle-dependent alteration in NAC1 nuclear body dynamics and morphology. Phys. Biol. 8, 015005 (2011). 21301057 PMC3164573
- [15]Lee M. H., Wu P. H., Gilkes D., Aifuwa I., Wirtz D., Normal mammary epithelial cells promote carcinoma basement membrane invasion by inducing microtubule-rich protrusions. Oncotarget 6, 32634– 32645 (2015). 26334095 PMC4741718
- [17]Phillip J. M., Wu P. H., Gilkes D. M., Williams W., McGovern S., Daya J., Chen J., Aifuwa I., Lee J. S. H., Fan R., Walston J., Wirtz D., Biophysical and biomolecular determination of cellular age in humans. Nat. Biomed. Eng. 1, 0093 (2017). 31372309 PMC6675017
- [18]Yong K. M. A., Zeng Y., Vindivich D., Phillip J. M., Wu P. H., Wirtz D., Getzenberg R. H., Morphological effects on expression of growth differentiation factor 15 (GDF15), a marker of metastasis. J. Cell. Physiol. 229, 362– 373 (2014). 23996089 PMC4492540
- [19]Minn A. J., Gupta G. P., Siegel P. M., Bos P. D., Shu W., Giri D. D., Viale A., Olshen A. B., Gerald W. L., Massagué J., Genes that mediate breast cancer metastasis to lung. Nature 436, 518– 524 (2005). 16049480 PMC1283098
- [20]Maine E. A., Westcott J. M., Prechtl A. M., Dang T. T., Whitehurst A. W., Pearson G. W., The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion. Oncotarget 7, 14708– 14726 (2016). 26895102 PMC4924746
- [21]Pishvaian M. J., Feltes C. M., Thompson P., Bussemakers M. J., Schalken J. A., Byers S. W., Cadherin-11 is expressed in invasive breast cancer cell lines. Cancer Res. 59, 947– 952 (1999). 10029089
- [22]Martin T. A., Watkins G., Jiang W. G., KiSS-1 expression in human breast cancer. Clin. Exp. Metastas. 22, 503– 511 (2005). 16320113
- [23]Kim J., Reber H. A., Hines O. J., Kazanjian K. K., Tran A., Ye X., Amersi F. F., Martinez S. R., Dry S. M., Bilchik A. J., Hoon D. S. B., The clinical significance of MAGEA3 expression in pancreatic cancer. Int. J. Cancer 118, 2269– 2275 (2006). 16331618
- [24]Kruger S., Ola V., Feller A. C., Fischer D., Friedrich M., Expression of cancer-testis antigen CT7 (MAGE-C1) in breast cancer: An immunohistochemical study with emphasis on prognostic utility. Pathol. Oncol. Res. 13, 91– 96 (2007). 17607369
- [25]Kuribayashi K., Krigsfeld G., Wang W., Xu J., Mayes P. A., Dicker D. T., Wu G. S., El-Deiry W. S., TNFSF10 (TRAIL), a p53 target gene that mediates p53-dependent cell death. Cancer Biol. Ther. 7, 2034– 2038 (2014). 19106633
- [26]Muller A., Homey B., Soto H., Ge N., Catron D., Buchanan M. E., McClanahan T., Murphy E., Yuan W., Wagner S. N., Barrera J. L., Mohar A., Verástegui E., Zlotnik A., Involvement of chemokine receptors in breast cancer metastasis. Nature 410, 50– 56 (2001). 11242036
- [27]Ashburner M., Ball C. A., Blake J. A., Botstein D., Butler H., Cherry J. M., Davis A. P., Dolinski K., Dwight S. S., Eppig J. T., Harris M. A., Hill D. P., Issel-Tarver L., Kasarskis A., Lewis S., Matese J. C., Richardson J. E., Ringwald M., Rubin G. M., Sherlock G., Gene Ontology: Tool for the unification of biology. Nat. Genet. 25, 25– 29 (2000). 10802651 PMC3037419
- [28]Gene Ontology Consortium, Gene Ontology Consortium: Going forward. Nucleic Acids Res. 43, D1049– D1056 (2015). 25428369 PMC4383973
- [29]Carbon S., Ireland A., Mungall C. J., Shu S. Q., Marshall B., Lewis S.; the AmiGO Hub; the Web Presence Working Group, AmiGO: Online access to ontology and annotation data. Bioinformatics 25, 288– 289 (2009). 19033274 PMC2639003
- [31]Watanabe T., Tanaka Y., Age-related alterations in the size of human hepatocytes. A study of mononuclear and binucleate cells. Virchows Arch. B. Cell Pathol. Icnl. Mol. Pathol. 39, 9– 20 (1982). 6123185
- [32]Conlon I., Raff M., Size control in animal development. Cell 96, 235– 244 (1999). 9988218
- [33]Frankfurt O. S., Slocum H. K., Rustum Y. M., Arbuck S. G., Pavelic Z. P., Petrelli N., Huben R. P., Pontes E. J., Greco W. R., Flow cytometric analysis of DNA aneuploidy in primary and metastatic human solid tumors. Cytometry 5, 71– 80 (1984). 6199167
- [34]Korenaga D., Okamura T., Saito A., Baba H., Sugimachi K., DNA Ploidy Is Closely linked to tumor invasion, lymph-node metastasis, and prognosis in clinical gastric-cancer. Cancer 62, 309– 313 (1988). 3383131
- [35]Navin N., Kendall J., Troge J., Andrews P., Rodgers L., McIndoo J., Cook K., Stepansky A., Levy D., Esposito D., Muthuswamy L., Krasnitz A., McCombie W. R., Hicks J., Wigler M., Tumour evolution inferred by single-cell sequencing. Nature 472, 90– 94 (2011). 21399628 PMC4504184
- [36]Pavelka N., Rancati G., Li R., Dr Jekyll and Mr Hyde: Role of aneuploidy in cellular adaptation and cancer. Curr. Opin. Cell Biol. 22, 809– 815 (2010). 20655187 PMC2974767
- [37]Fraley S. I., Feng Y., Krishnamurthy R., Kim D. H., Celedon A., Longmore G. D., Wirtz D., A distinctive role for focal adhesion proteins in three-dimensional cell motility. Nat. Cell Biol. 12, 598– 604 (2010). 20473295 PMC3116660
- [38]Fraley S. I., Wu P. H., He L., Feng Y., Krisnamurthy R., Longmore G. D., Wirtz D., Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP utility by spatially and temporally directing protrusions. Sci. Rep. 5, 14580 (2015). 26423227 PMC4589685
- [39]Wu P. H., Giri A., Sun S. X., Wirtz D., Three-dimensional cell migration does not follow a random walk. Proc. Natl. Acad. Sci. U.S.A. 111, 3949– 3954 (2014). 24594603 PMC3964056
- [40]Wu P. H., Giri A., Wirtz D., Statistical analysis of cell migration in 3D using the anisotropic persistent random walk model. Nat. Protoc. 10, 517– 527 (2015). 25719270 PMC4911638
- [41]Ringner M., Fredlund E., Hakkinen J., Borg A., Staaf J., GOBO: gene expression-based outcome for breast cancer online. PLOS ONE 6, e17911 (2011). 21445301 PMC3061871
- [42]Lee M. H., Wu P. H., Staunton J. R., Ros R., Longmore G. D., Wirtz D., Mismatch in mechanical and adhesive properties induces pulsating cancer cell migration in epithelial monolayer. Biophys. J. 102, 2731– 2741 (2012). 22735523 PMC3379010
- [43]Guo Q. Y., Phillip J. M., Majumdar S., Wu P. H., Chen J., Calderón-Colón X., Schein O., Smith B. J., Trexler M. M., Wirtz D., Elisseeff J. H., Modulation of keratocyte phenotype by collagen fibril nanoarchitecture in membranes for corneal repair. Biomaterials 34, 9365– 9372 (2013). 24041426 PMC8086596
- [44]Deng W., Tsao S. W., Lucas J. N., Leung C. S., Cheung A. L. M., A new method for improving metaphase chromosome spreading. Cytom. Part. A 51A, 46– 51 (2003). 12500304
- [45]Potapova T. A., Unruh J. R., Box A. C., Bradford W. D., Seidel C. W., Slaughter B. D., Sivagnanam S., Wu Y., Li R., Karyotyping human and mouse cells using probes from single-sorted chromosomes and open source software. Biotechniques 59, 335– 346 (2015). 26651513
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Neri, F., Zheng, S., Watson, M. A., Desprez, P.-Y., Gerencser, A. A., Campisi, J., Wirtz, D., Wu, P.-H., & Schilling, B. (2025) · Aging · doi:10.18632/aging.206299 · Cited by 6 · see citing works
Self-citation
- Authors
- Wu, P.-H., Gilkes, D. M., Phillip, J. M., Narkar, A., Cheng, T. W.-T., Marchand, J., Lee, M.-H., Li, R., & Wirtz, D.
- Affiliations
- Johns Hopkins University (US)
- Boston University (US)
- Corresponding author
- Wu, Pei-Hsun
- Wirtz, Denis
- ORCID
- Venue
- Science Advances
- Published
- 2020-01-24
- Volume
- 6
- Issue
- 4
- Pages
- eaaw6938-eaaw6938
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC6976289
- OpenAlex
- W3001425747
- Cited by
- 177
- References
- 4
- Citations by year
- 2026: 12 · 2025: 42 · 2024: 35 · 2023: 22 · 2022: 34 · 2021: 23 · 2020: 9
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by-nc)
- Funders
- National Cancer Institute (U54CA143868, R01CA174388)
- National Institute of General Medical Sciences (R35GM118172)
- National Institute of Neurological Disorders and Stroke (R21NS087485)
- American Heart Association (12POST12050638)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- cell morphology, breast cancer, metastasis, single-cell clones, nuclear morphology, tumorigenicity, precision medicine
- MeSH terms
- Animals, Breast Neoplasms, Female, Humans, Neoplasm Metastasis, Neoplasm Staging, Phenotype, Prognosis, Biomarkers, Tumor, Disease Progression, Gene Expression Profiling, Cell Line, Tumor, Mice, Single-Cell Analysis, Transcriptome
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