Spatiotemporal view of malignant histogenesis and macroevolution via formation of polyploid giant cancer cells DOI Creative Commons
Xiaoran Li, Yanping Zhong, Xudong Zhang

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(9), P. 665 - 678

Published: Jan. 3, 2023

Abstract To understand how malignant tumors develop, we tracked cell membrane, nuclear spindle, and cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single underwent traditional mitosis to generate tissue with uniform size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, fusion, karyokinesis without cytokinesis. restitution fragmentation, micronuclei increase contents heterogeneity. At cellular level, development was associated forming transient intracellular cells, termed fecundity cells. The can be decellularized facilitate fusion synchronized other nuclei for subsequent replication. undergo several rounds entosis form complex structures, structures. multiple modes replication absence cytokinesis leads an nuclear-to-cytoplasmic (N/C) ratio reproduction, which is remarkably similar mode division pre-embryogenesis. Our data support that may represent a central regulator histogenesis, intratumoral heterogeneity, immune escape, macroevolution de-repression suppressed pre-embryogenic program somatic

Language: Английский

Polyploidy DOI Creative Commons

Laura E. Frawley,

Terry L. Orr‐Weaver

Current Biology, Journal Year: 2015, Volume and Issue: 25(9), P. R353 - R358

Published: May 1, 2015

Language: Английский

Citations

96

Essential role for a novel population of binucleated mammary epithelial cells in lactation DOI Creative Commons
Anne C. Rios, Nai Yang Fu,

Paul R. Jamieson

et al.

Nature Communications, Journal Year: 2016, Volume and Issue: 7(1)

Published: April 22, 2016

The mammary gland represents a unique tissue to study organogenesis as it predominantly develops in the post-natal animal and undergoes dramatic morphogenetic changes during puberty reproductive cycle. physiological function of is produce milk sustain newborn. Here we view lactating through three-dimensional confocal imaging intact tissue. We observed that majority secretory alveolar cells are binucleated. These first arise very late pregnancy due failure cytokinesis larger than mononucleated cells. Augmented expression Aurora kinase-A Polo-like kinase-1 at lactogenic switch likely mediates formation binucleated Our findings demonstrate an important role for polyploid epithelial lactation, based on their presence five different species, suggest evolved maximize production promote survival offspring across all mammalian species.

Language: Английский

Citations

93

Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells DOI Creative Commons
Kenneth J. Pienta, Emma U. Hammarlund, Joel S. Brown

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(7)

Published: Jan. 27, 2021

We present a unifying theory to explain cancer recurrence, therapeutic resistance, and lethality. The basis of this is the formation simultaneously polyploid aneuploid cells, polyaneuploid cells (PACCs), that avoid toxic effects systemic therapy by entering state cell cycle arrest. independent which classically associated oncogenic mutations have already occurred. PACCs been generally disregarded as senescent or dying cells. Our states resistance driven PACC enabled accessing program allows an double its genomic content, followed entry into nondividing protect DNA integrity ensure survival. Upon removal stress, e.g., chemotherapy, undergo depolyploidization generate resistant progeny make up bulk within tumor.

Language: Английский

Citations

92

Soma-to-germline RNA communication DOI
Colin C. Conine, Oliver J. Rando

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 23(2), P. 73 - 88

Published: Sept. 20, 2021

Language: Английский

Citations

58

Spatiotemporal view of malignant histogenesis and macroevolution via formation of polyploid giant cancer cells DOI Creative Commons
Xiaoran Li, Yanping Zhong, Xudong Zhang

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(9), P. 665 - 678

Published: Jan. 3, 2023

Abstract To understand how malignant tumors develop, we tracked cell membrane, nuclear spindle, and cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single underwent traditional mitosis to generate tissue with uniform size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, fusion, karyokinesis without cytokinesis. restitution fragmentation, micronuclei increase contents heterogeneity. At cellular level, development was associated forming transient intracellular cells, termed fecundity cells. The can be decellularized facilitate fusion synchronized other nuclei for subsequent replication. undergo several rounds entosis form complex structures, structures. multiple modes replication absence cytokinesis leads an nuclear-to-cytoplasmic (N/C) ratio reproduction, which is remarkably similar mode division pre-embryogenesis. Our data support that may represent a central regulator histogenesis, intratumoral heterogeneity, immune escape, macroevolution de-repression suppressed pre-embryogenic program somatic

Language: Английский

Citations

34