Senescent tumor cells lead the collective invasion in thyroid cancer

Kim, Young Hwa; Choi, Yong Won; Lee, Jeonghun; Soh, Euy Young; Kim, Jang-Hee; Park, Tae Jun

doi:10.1038/ncomms15208

Cited by 185 publications

(225 citation statements)

References 53 publications

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“…10,11 We evaluated the transcription of three well-characterized SASP-associated genes, IL8, CXCL1, and PAI1. CYCLA2 (cyclin A) was also evaluated to confirm proliferative arrest.…”

Section: Resultsmentioning

confidence: 99%

Improved Dose-Response Relationship of (+)-Discodermolide-Taxol Hybrid Congeners

et al. 2018

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(+)-Discodermolide is a microtubule-stabilizing agent with potential for the treatment of taxol-refractory malignancies. (+)-Discodermolide congeners containing the C-3′-phenyl side chain of taxol (paclitaxel) were synthesized based on computational docking models predicting this moiety would fill an aromatic pocket of β-tubulin insufficiently occupied by (+)-discodermolide, thereby conferring improved ligand–target interaction. It was recently demonstrated, however, that the C-3′-phenyl side chain occupied a different space, instead extending toward the M-loop of β-tubulin, where it induced a helical conformation, hypothesized to improve lateral contacts between adjacent microtubule protofilaments. This insight led us to evaluate the biological activity of hybrid congeners using a panel of genetically diverse cancer cell lines. Hybrid molecules retained the same tubulin-polymerizing profile as (+)-discodermolide. Since (+)-discodermolide is a potent inducer of accelerated senescence, a fate that contributes to drug resistance, congeners were also screened for senescence induction. Flow cytometric and transcriptional analysis revealed that the hybrids largely retained the senescence-inducing properties of (+)-discodermolide. In taxol-sensitive cell models, the congeners had improved dose-response parameters relative to (+)-discodermolide and, in some cases, were superior to taxol. However, in cells susceptible to senescence, EMax increased without concomitant improvements in EC50 such that overall dose-response profiles resembled that of (+)-discodermolide.

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“…10,11 We evaluated the transcription of three well-characterized SASP-associated genes, IL8, CXCL1, and PAI1. CYCLA2 (cyclin A) was also evaluated to confirm proliferative arrest.…”

Section: Resultsmentioning

confidence: 99%

Improved Dose-Response Relationship of (+)-Discodermolide-Taxol Hybrid Congeners

et al. 2018

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“…For example, senescent tumor cells in papillary thyroid carcinoma (PTC) have high invasion potential through the SASP and are involved in lymph node metastasis. Mechanically, upregulated CXCL12/CXCR4 signaling plays a crucial role in the invasion of PTC cells by graded expression near the invasion border (Y. H. Kim et al, ).…”

Section: Cellular Senescence and Neurodegenerative Diseasesmentioning

confidence: 99%

Cellular senescence: Molecular mechanisms and pathogenicity

Wei

2018

Journal Cellular Physiology

153

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Cellular senescence is the arrest of normal cell division. Oncogenic genes and oxidative stress, which cause genomic DNA damage and generation of reactive oxygen species, lead to cellular senescence. The senescence-associated secretory phenotype is a distinct feature of senescence. Senescence is normally involved in the embryonic development. Senescent cells can communicate with immune cells to invoke an immune response. Senescence emerges during the aging process in several tissues and organs. In fact, increasing evidence shows that cellular senescence is implicated in aging-related diseases, such as nonalcoholic fatty liver disease, obesity and diabetes, pulmonary hypertension, and tumorigenesis. Cellular senescence can also be induced by microbial infection. During cellular senescence, several signaling pathways, including those of p53, nuclear factor-κB (NF-κB), mammalian target of rapamycin, and transforming growth factor-beta, play important roles. Accumulation of senescent cells can trigger chronic inflammation, which may contribute to the pathological changes in the elderly. Given the variety of deleterious effects caused by cellular senescence in humans, strategies have been proposed to control senescence. In this review, we will focus on recent studies to provide a brief introduction to cellular senescence, including associated signaling pathways and pathology.

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“…In fact, tumors also contain multiple subpopulations of tumor cells with distinct genotypic and phenotypic characteristics . Importantly, this cellular heterogeneity is associated with differences in metastatic potential and therapeutic response . It remains unclear how these subpopulations of cancer cells contribute to collective invasion.…”

Section: Introductionmentioning

confidence: 99%

Cancer stem‐like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion

Quan

Wang

et al. 2020

Cancer Science

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Collective invasion of cancer cells is the key process of circulating tumor cell (CTC) cluster formation, and greatly contributes to metastasis. Cancer stem-like cells (CSC) have a distinct advantage of motility for metastatic dissemination. To verify the role of CSC in the collective invasion, we performed 3D assays to investigate the collective invasion from cancer cell spheroids. The results demonstrated that CSC can significantly promote both collective and single-cell invasion. Further study showed that CSC prefer to move outside and lead the collective invasion. More interestingly, approximately 60% of the leader CSC in collective invasion co-expressed both epithelial and mesenchymal genes, while only 4% co-expressed in single invasive CSC, indicating that CSC with hybrid epithelial/mesenchymal phenotype play a key role in cancer cell collective invasion. K E Y W O R D Scancer stem-like cells, collective invasion, hybrid epithelial/mesenchymal, leader, single invasion

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Senescent tumor cells lead the collective invasion in thyroid cancer

Cited by 185 publications

References 53 publications

Improved Dose-Response Relationship of (+)-Discodermolide-Taxol Hybrid Congeners

Improved Dose-Response Relationship of (+)-Discodermolide-Taxol Hybrid Congeners

Cellular senescence: Molecular mechanisms and pathogenicity

Cancer stem‐like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion

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