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Journal ArticleDOI

Giant cells: Linking McClintock's heredity to early embryogenesis and tumor origin throughout millennia of evolution on Earth.

TL;DR: Giant cells link McClintock's heredity to both early embryogenesis and tumor origin, the most fundamental mechanism on how both germ and soma for coping with environmental stresses for the survival across the tree of life which evolved over millions of years on Earth.
About: This article is published in Seminars in Cancer Biology.The article was published on 2021-06-08. It has received 16 citations till now. The article focuses on the topics: Biology & Heredity.
Citations
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Journal ArticleDOI
29 Sep 2021
TL;DR: In this article, the role of polyploid giant cancer cells (PGCCs) in drug resistance and disease relapse was examined by examining the mRNA expression profile of PGCCs following treatment with paclitaxel in ovarian cancer cells.
Abstract: To understand the role of polyploid giant cancer cells (PGCCs) in drug resistance and disease relapse, we examined the mRNA expression profile of PGCCs following treatment with paclitaxel in ovarian cancer cells. An acute activation of IL-6 dominated senescence-associated secretory phenotype lasted 2-3 weeks and declined during the termination phase of polyploidy. IL-6 activates embryonic stemness during the initiation of PGCCs and can reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) via increased collagen synthesis, activation of VEGF expression, and enrichment of CAFs and the GPR77 + /CD10 + fibroblast subpopulation. Blocking the IL-6 feedback loop with tocilizumab or apigenin prevented PGCC formation, attenuated embryonic stemness and the CAF phenotype, and inhibited tumor growth in a patient-derived xenograft high-grade serous ovarian carcinoma model. Thus, IL-6 derived by PGCCs is capable of reprogramming both cancer and stromal cells and contributes to the evolution and remodeling of cancer. Targeting IL-6 in PGCCs may represent a novel approach to combating drug resistance.

19 citations

Journal ArticleDOI
TL;DR: In this article , the authors report the biological properties of PGCC, including mitochondrial alterations, and reveal that autophagy is a critical mechanism for PGCC induction, and suggest a therapeutic approach of targeting dormant PGCCs in cancer.
Abstract: Abstract Dormant cancer cells that survive anticancer therapy can lead to cancer recurrence and disseminated metastases that prove fatal in most cases. Recently, specific dormant polyploid giant cancer cells (PGCC) have drawn our attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In this study, we report the biological properties of PGCC, including mitochondrial alterations, and reveal that autophagy is a critical mechanism of PGCC induction. Moreover, pharmacologic or genetic inhibition of autophagy greatly impaired PGCC formation, significantly suppressing metastasis and improving survival in a mouse model. Mechanistically, chemotherapeutic drugs partly damaged mitochondria, which then produced low ATP levels and activated autophagy via the AMPK-mTOR pathway to promote PGCC formation. Analysis of the transcriptional and epigenetic landscape of PGCC revealed overexpression of RIPK1, and the scaffolding function of RIPK1 was required for AMPK-mTOR pathway-induced PGCC survival. High numbers of PGCCs correlated with shorter recurrence time and worse survival outcomes in patients with NPC. Collectively, these findings suggest a therapeutic approach of targeting dormant PGCCs in cancer. Significance: Pretreatment with an autophagy inhibitor before chemotherapy could prevent formation of therapy-induced dormant polyploid giant cancer cells, thereby reducing recurrence and metastasis of nasopharyngeal carcinoma.

17 citations

Journal ArticleDOI
TL;DR: In this paper, the key mechanisms that regulate the different stages of the giant cell life cycle have been investigated, and new opportunities for therapeutic intervention have been proposed for tumor cell activation and dedifferentiation.

14 citations

Journal ArticleDOI
TL;DR: The giant cell life cycle, a recently proposed mechanism for malignant transformation of somatic cells, has been studied in this paper , which can lead to the formation of polyploid giant cancer cells, activation of an early embryonic program, and dedifferentiation of cells.

13 citations

References
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Journal ArticleDOI
James D. Watson1, Francis Crick1
25 Apr 1953-Nature
TL;DR: The determination in 1953 of the structure of deoxyribonucleic acid (DNA), with its two entwined helices and paired organic bases, was a tour de force in X-ray crystallography and opened the way for a deeper understanding of perhaps the most important biological process.
Abstract: The determination in 1953 of the structure of deoxyribonucleic acid (DNA), with its two entwined helices and paired organic bases, was a tour de force in X-ray crystallography. But more significantly, it also opened the way for a deeper understanding of perhaps the most important biological process. In the words of Watson and Crick: "It has not escaped our notice that the specific pairing that we have postulated immediately suggests a possible copying mechanism for the genetic material." [Obituary of Francis Crick:

9,946 citations

Journal ArticleDOI
Patrick S. Schnable1, Doreen Ware2, Robert S. Fulton3, Joshua C. Stein2  +156 moreInstitutions (18)
20 Nov 2009-Science
TL;DR: The sequence of the maize genome reveals it to be the most complex genome known to date and the correlation of methylation-poor regions with Mu transposon insertions and recombination and how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state is reported.
Abstract: We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.

3,761 citations

Journal ArticleDOI
16 Nov 1984-Science
TL;DR: An attempt is made to outline several experiments conducted by the author that revealed how a genome may react to conditions for which it is unprepared, but to which it responds in a discernible, but initially unforeseen manner.
Abstract: An attempt is made to outline several experiments conducted by the author that revealed how a genome may react to conditions for which it is unprepared, but to which it responds in a discernible, but initially unforeseen manner. One of the experiments involves the effect of X-rays on chromosomes of maize. 35 references, 3 figures.

2,293 citations