{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T19:58:01Z","timestamp":1774727881396,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009596","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000}}],"reference-count":143,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Cancer reflects the dysregulation of the underlying gene network, which is strongly related to the 3D genome organization. Numerous efforts have been spent on experimental characterizations of the structural alterations in cancer genomes. However, there is still a lack of genomic structural-level understanding of the temporal dynamics for cancer initiation and progression. Here, we use a landscape-switching model to investigate the chromosome structural transition during the cancerization and reversion processes. We find that the chromosome undergoes a non-monotonic structural shape-changing pathway with initial expansion followed by compaction during both of these processes. Furthermore, our analysis reveals that the chromosome with a more expanding structure than those at both the normal and cancer cell during cancerization exhibits a sparse contact pattern, which shows significant structural similarity to the one at the embryonic stem cell in many aspects, including the trend of contact probability declining with the genomic distance, the global structural shape geometry and the spatial distribution of loci on the chromosome. In light of the intimate structure-function relationship at the chromosomal level, we further describe the cell state transition processes by the chromosome structural changes, suggesting an elevated cell stemness during the formation of the cancer cells. We show that cell cancerization and reversion are highly irreversible processes in terms of the chromosome structural transition pathways, spatial repositioning of chromosomal loci and hysteresis loop of contact evolution analysis. Our model draws a molecular-scale picture of cell cancerization from the chromosome structural perspective. The process contains initial reprogramming towards the stem cell followed by the differentiation towards the cancer cell, accompanied by an initial increase and subsequent decrease of the cell stemness.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009596","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T14:03:02Z","timestamp":1636466582000},"page":"e1009596","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Deciphering the molecular mechanism of the cancer formation by chromosome structural 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Cesari","year":"2018","journal-title":"Computation"},{"issue":"19","key":"pcbi.1009596.ref072","doi-asserted-by":"crossref","first-page":"6062","DOI":"10.1073\/pnas.1506257112","article-title":"Topology, structures, and energy landscapes of human chromosomes","volume":"112","author":"B Zhang","year":"2015","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"24","key":"pcbi.1009596.ref073","doi-asserted-by":"crossref","first-page":"248101","DOI":"10.1103\/PhysRevLett.116.248101","article-title":"Shape transitions and chiral symmetry breaking in the energy landscape of the mitotic chromosome","volume":"116","author":"B Zhang","year":"2016","journal-title":"Physical review letters"},{"issue":"1","key":"pcbi.1009596.ref074","doi-asserted-by":"crossref","first-page":"010901","DOI":"10.1063\/5.0044150","article-title":"Multiscale modeling of genome organization with maximum entropy optimization","volume":"155","author":"X Lin","year":"2021","journal-title":"The 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Bjerkvig","year":"2005","journal-title":"Nature Reviews Cancer"},{"issue":"11","key":"pcbi.1009596.ref114","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1093\/emboj\/20.11.2907","article-title":"Engineered interphase chromosome loops guide intrachromosomal recombination","volume":"20","author":"R Kostriken","year":"2001","journal-title":"The EMBO journal"},{"issue":"6","key":"pcbi.1009596.ref115","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.cell.2012.03.051","article-title":"Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor","volume":"149","author":"W Deng","year":"2012","journal-title":"Cell"},{"issue":"1","key":"pcbi.1009596.ref116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms15993","article-title":"Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping","volume":"8","author":"SL Morgan","year":"2017","journal-title":"Nature 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collective tumor cell dissemination and metastatic aggressiveness of inflammatory breast cancer","volume":"8","author":"S Tripathi","year":"2018","journal-title":"Frontiers in oncology"},{"issue":"13","key":"pcbi.1009596.ref127","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1158\/0008-5472.CAN-14-3476","article-title":"Tracking and functional characterization of epithelial\u2013mesenchymal transition and mesenchymal tumor cells during prostate cancer metastasis","volume":"75","author":"M Ruscetti","year":"2015","journal-title":"Cancer research"},{"issue":"5","key":"pcbi.1009596.ref128","article-title":"The EMT universe: space between cancer cell dissemination and metastasis initiation","volume":"19","author":"L Ombrato","year":"2014","journal-title":"Critical Reviews in Oncogenesis"},{"issue":"3","key":"pcbi.1009596.ref129","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.tcb.2018.12.001","article-title":"EMT transition states during tumor progression and 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Zhang","year":"2019","journal-title":"The Journal of Physical Chemistry B"},{"issue":"5","key":"pcbi.1009596.ref136","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrg.2016.13","article-title":"Epigenetic modulators, modifiers and mediators in cancer aetiology and progression","volume":"17","author":"AP Feinberg","year":"2016","journal-title":"Nature Reviews Genetics"},{"issue":"8","key":"pcbi.1009596.ref137","doi-asserted-by":"crossref","first-page":"e1000153","DOI":"10.1371\/journal.pcbi.1000153","article-title":"Structure and dynamics of interphase chromosomes","volume":"4","author":"A Rosa","year":"2008","journal-title":"PLoS computational biology"},{"issue":"1","key":"pcbi.1009596.ref138","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0167-4781(87)90040-6","article-title":"Recent studies of DNA topoisomerases","volume":"909","author":"JC Wang","year":"1987","journal-title":"Biochimica et Biophysica Acta (BBA)-Gene Structure and 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