Heat Stress-Induced Multiple Multipolar Divisions of Human Cancer Cells

Chen, Shaoyong; Liu, Mingyue; Huang, Haohai; Li, Bo; Zhao, Hang; Feng, Xi‐Qiao; Zhao, Hongping

doi:10.3390/cells8080888

Cited by 9 publications

(4 citation statements)

References 60 publications

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“…The misalignment of chromosomes followed by mitotic slippage is known to induce G1 arrest and cell death [53]. Hyperthermia produces chromosomal misalignment and mitotic slippage in cells [54,55]. However, the underlying mechanism for the chromosome misalignment is yet to be understood.…”

Section: Prolonged Hyperthermia Leads To Chromosomal Misalignment In mentioning

confidence: 99%

Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells

Mundhara

Majumder

Panda

2021

Biochemical Journal

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Human body temperature limits below 40°C during heat stroke or fever. The implications of prolonged exposure to the physiologically relevant temperature (40°C) on cellular mechanobiology is poorly understood. Here, we have examined the effects of heat stress (40°C for 72 h incubation) in human lung adenocarcinoma (A549), mouse melanoma (B16F10), and non-cancerous mouse origin adipose tissue cells (L929). Hyperthermia increased the level of ROS, γ-H2AX and HSP70 and decreased mitochondrial membrane potential in the cells. Heat stress impaired cell division, caused G1 arrest, induced cellular senescence, and apoptosis in all the tested cell lines. The cells incubated at 40°C for 72 h displayed a significant decrease in the f-actin level and cellular traction as compared with cells incubated at 37°C. Also, the cells showed a larger focal adhesion area and stronger adhesion at 40°C than at 37°C. The mitotic cells at 40°C were unable to round up properly and displayed retracting actin stress fibers. Hyperthermia down-regulated HDAC6, increased the acetylation level of microtubules, and perturbed the chromosome alignment in the mitotic cells at 40°C. Overexpression of HDAC6 rescued the cells from the G1 arrest and reduced the delay in cell rounding at 40°C suggesting a crucial role of HDAC6 in hyperthermia mediated responses. This study elucidates the significant role of cellular traction, focal adhesions, and cytoskeletal networks in mitotic cell rounding and chromosomal misalignment. It also highlights the significance of HDAC6 in heat-evoked senile cellular responses.

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Section: Prolonged Hyperthermia Leads To Chromosomal Misalignment In mentioning

confidence: 99%

Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells

Mundhara

Majumder

Panda

2021

Biochemical Journal

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“…These findings are related to cancer, as heat-stressed cells resemble the cancer phenotype; at the same time, heat treatment is a potential therapy for the treatment of tumors. Heat treatment has been long regarded as an important treatment option for cancer [ 60 ]; however, there are cons involving heat treatment, e.g., studies have reported multipolar divisions in cancer cells, ultimately facilitating tumor heterogeneity [ 61 ]. An interplay of the energy metabolic dynamism was reported in hyperthermia-resistant ovarian cancer cells [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Joint Transcriptome and Metabolome Analysis Prevails the Biological Mechanisms Underlying the Pro-Survival Fight in In Vitro Heat-Stressed Granulosa Cells

Sammad

Luo

et al. 2022

Biology

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Previous studies reported the physical, transcriptome, and metabolome changes in in vitro acute heat-stressed (38 °C versus 43 °C for 2 h) bovine granulosa cells. Granulosa cells exhibited transient proliferation senescence, oxidative stress, an increased rate of apoptosis, and a decline in steroidogenic activity. In this study, we performed a joint integration and network analysis of metabolomic and transcriptomic data to further narrow down and elucidate the role of differentially expressed genes, important metabolites, and relevant cellular and metabolic pathways in acute heat-stressed granulosa cells. Among the significant (raw p-value < 0.05) metabolic pathways where metabolites and genes converged, this study found vitamin B6 metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism, arginine biosynthesis, tryptophan metabolism, arginine and proline metabolism, histidine metabolism, and glyoxylate and dicarboxylate metabolism. Important significant convergent biological pathways included ABC transporters and protein digestion and absorption, while functional signaling pathways included cAMP, mTOR, and AMPK signaling pathways together with the ovarian steroidogenesis pathway. Among the cancer pathways, the most important pathway was the central carbon metabolism in cancer. Through multiple analysis queries, progesterone, serotonin, citric acid, pyridoxal, L-lysine, succinic acid, L-glutamine, L-leucine, L-threonine, L-tyrosine, vitamin B6, choline, and CYP1B1, MAOB, VEGFA, WNT11, AOX1, ADCY2, ICAM1, PYGM, SLC2A4, SLC16A3, HSD11B2, and NOS2 appeared to be important enriched metabolites and genes, respectively. These genes, metabolites, and metabolic, cellular, and cell signaling pathways comprehensively elucidate the mechanisms underlying the intricate fight between death and survival in acute heat-stressed bovine granulosa cells and essentially help further our understanding (and will help the future quest) of research in this direction.

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“…These findings are very related to cancer, as heat stressed cells resembles the cancer phenotype and at the same time heat treatment is a potential therapy for treatment of tumors. Heat treatment is long regarded as an important treatment option for cancer [56], however, there cons of heat treatment too, like studies reporting multipolar divisions in cancer cells, ultimately facilitating tumor heterogeneity [57]. An interplay of energy metabolic dynamism is reported in hyperthermia-resistant ovarian cancer cells [58].…”

Section: Discussionmentioning

confidence: 99%

Joint Transcriptome and Metabolome Analysis Prevails Biological Mechanisms Underlying the Prosurvival Fight in Heat Stressed Granulosa Cells

Sammad¹,

Luo²,

Hu³

et al. 2022

Preprint

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Previous studies reported the physical, transcriptomics and metabolomics changes in in-vitro acute heat stressed bovine granulosa cells. Granulosa cells exhibited transient proliferation senescence, oxidative stress, increased rate of apoptosis, and decline in steroidogenic activity. This study performs joint integration and network analysis of metabolomics and transcriptomics data to further narrow down and elucidate the role of differentially expressed genes, important metab-olites and relevant cellular and metabolic pathways in acute heat-stressed granulosa cells. Among significant (Raw P-value <0.05) metabolic pathways where metabolites and genes did converge, this study found Vitamin B6 metabolism, Glycine, serine and threonine metabolism, Phenylalanine metabo-lism, Arginine biosynthesis, Tryptophan metabolism, Arginine and proline metabolism, Histidine metabolism, and Glyoxylate and dicarboxylate metabolism. Important significant convergent bio-logical pathways included, ABC transporters and Protein digestion and absorption, while func-tional signaling pathways included cAMP, mTOR, and AMPK signaling pathways together with Ovarian steroidogenesis pathway. Among caner pathways, the most important pathway was Central carbon metabolism in cancer. Through multiple analysis query, Progesterone, Serotonin, citric acid, Pyridoxal, L-Lysine, Succinic acid, L-Glutamine, L-Leucine, L-Threonine, L-Tyrosine, Vitamin B6, Choline, and CYP1B1, MAOB, VEGFA, WNT11, AOX1, ADCY2, ICAM1, PYGM, SLC2A4, SLC16A3, HSD11B2 and NOS2 appeared to be important enriched metabolites and genes, respectively. These genes, metabolites, metabolic, cellular and cell signaling pathways com-prehensively elucidate the mechanisms underlying the intricate fight between death and survival in acute heat-stressed bovine granulosa cells, and essentially help further our understanding and future quest of research in this direction.

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Heat Stress-Induced Multiple Multipolar Divisions of Human Cancer Cells

Cited by 9 publications

References 60 publications

Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells

Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells

Joint Transcriptome and Metabolome Analysis Prevails the Biological Mechanisms Underlying the Pro-Survival Fight in In Vitro Heat-Stressed Granulosa Cells

Joint Transcriptome and Metabolome Analysis Prevails Biological Mechanisms Underlying the Prosurvival Fight in Heat Stressed Granulosa Cells

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