scholarly journals Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

2020 ◽  
Vol 61 (5) ◽  
pp. 611-635 ◽  
Author(s):  
Faustino Mollinedo ◽  
Consuelo Gajate
Keyword(s):  
Signal Transduction ◽  
Cell Death ◽  
Tumor Progression ◽  
Cell Survival ◽  
Cancer Cells ◽  
Lipid Rafts ◽  
Critical Role ◽  
Death Receptors ◽  
Signaling Molecules ◽  
Downstream Signaling

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

scholarly journals Assessment of the Impact of Post-Thaw Stress Pathway Modulation on Cell Recovery following Cryopreservation in a Hematopoietic Progenitor Cell Model

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 278
Author(s):  
John M. Baust ◽  
Kristi K. Snyder ◽  
Robert G. Van Buskirk ◽  
John G. Baust
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Survival ◽  
Critical Role ◽  
Hematopoietic Progenitor Cell ◽  
Scale Production ◽  
Cell Recovery ◽  
Hematopoietic Progenitor ◽  
Discovery Science ◽  
The Impact

The development and use of complex cell-based products in clinical and discovery science continues to grow at an unprecedented pace. To this end, cryopreservation plays a critical role, serving as an enabling process, providing on-demand access to biological material, facilitating large scale production, storage, and distribution of living materials. Despite serving a critical role and substantial improvements over the last several decades, cryopreservation often remains a bottleneck impacting numerous areas including cell therapy, tissue engineering, and tissue banking. Studies have illustrated the impact and benefit of controlling cryopreservation-induced delayed-onset cell death (CIDOCD) through various “front end” strategies, such as specialized media, new cryoprotective agents, and molecular control during cryopreservation. While proving highly successful, a substantial level of cell death and loss of cell function remains associated with cryopreservation. Recently, we focused on developing technologies (RevitalICE™) designed to reduce the impact of CIDOCD through buffering the cell stress response during the post-thaw recovery phase in an effort to improve the recovery of previously cryopreserved samples. In this study, we investigated the impact of modulating apoptotic caspase activation, oxidative stress, unfolded protein response, and free radical damage in the initial 24 h post-thaw on overall cell survival. Human hematopoietic progenitor cells in vitro cryopreserved in both traditional extracellular-type and intracellular-type cryopreservation freeze media were utilized as a model cell system to assess impact on survival. Our findings demonstrated that through the modulation of several of these pathways, improvements in cell recovery were obtained, regardless of the freeze media and dimethyl sulfoxide concentration utilized. Specifically, through the use of oxidative stress inhibitors, an average increase of 20% in overall viability was observed. Furthermore, the results demonstrated that by using the post-thaw recovery reagent on samples cryopreserved in intracellular-type media (Unisol™), improvements in overall cell survival approaching 80% of non-frozen controls were attained. While improvements in overall survival were obtained, an assessment on the impact of specific cell subpopulations and functionality remains to be completed. While work remains, these results represent an important step forward in the development of improved cryopreservation processes for use in discovery science, and commercial and clinical settings.

Abstract 3318: A critical role for c-Jun N-terminal kinase in autophagy and cell survival of breast cancer cells

2017 ◽  
Author(s):  
Rohit Munagala ◽  
Carol Joseph ◽  
Annie Liu ◽  
Kebin Liu ◽  
Muthusamy Thangaraju ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Role

scholarly journals ROS Mediate xCT-Dependent Cell Death in Human Breast Cancer Cells under Glucose Deprivation

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1598 ◽  
Author(s):  
Mei-Chun Chen ◽  
Li-Lin Hsu ◽  
Sheng-Fan Wang ◽  
Chih-Yi Hsu ◽  
Hsin-Chen Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Glucose Deprivation ◽  
Glutathione Biosynthesis ◽  
Dependent Cell ◽  
Amp Activated Protein Kinase

xCT, also known as solute carrier family 7 member 11 (SLC7A11), the light chain of the cystine/glutamate antiporter, is positively correlated with cancer progression due to antioxidant function. During glucose deprivation, the overexpression of xCT does not protect cancer cells but instead promotes cell death. Further understanding the mechanism of glucose deprivation-induced cell death is important for developing anticancer treatments targeting the glucose metabolism. In this study, we found that breast cancer cells with a high expression of xCT demonstrated increased levels of reactive oxygen species (ROS) and were more sensitive to glucose deprivation than the cells with a low expression of xCT. However, AMP-activated protein kinase (AMPK) did not significantly affect glucose-deprivation-induced cell death. The antioxidant N-acetyl-cysteine prevented glucose-deprivation-induced cell death, and the glutathione biosynthesis inhibitor L-buthionine-S, R-sulfoximine enhanced glucose-deprivation-induced cell death. The inhibition of xCT by sulfasalazine or a knockdown of xCT reduced the glucose-deprivation-increased ROS levels and glucose-deprivation-induced cell death. Glucose deprivation reduced the intracellular glutamate, and supplementation with α-ketoglutarate prevented the glucose-deprivation-increased ROS levels and rescued cell death. The knockdown of sirtuin-3 (SIRT3) further enhanced the ROS levels, and promoted xCT-related cell death after glucose deprivation. In conclusion, our results suggested that ROS play a critical role in xCT-dependent cell death in breast cancer cells under glucose deprivation.

scholarly journals Differential Effects of Endoplasmic Reticulum Stress-induced Autophagy on Cell Survival

2006 ◽  
Vol 282 (7) ◽  
pp. 4702-4710 ◽  
Author(s):  
Wen-Xing Ding ◽  
Hong-Min Ni ◽  
Wentao Gao ◽  
Yi-Feng Hou ◽  
Melissa A. Melan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Cell Survival ◽  
Cancer Cells ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Brefeldin A ◽  
Human Colon ◽  
The Impact

Autophagy is a cellular response to adverse environment and stress, but its significance in cell survival is not always clear. Here we show that autophagy could be induced in the mammalian cells by chemicals, such as A23187, tunicamycin, thapsigargin, and brefeldin A, that cause endoplasmic reticulum stress. Endoplasmic reticulum stress-induced autophagy is important for clearing polyubiquitinated protein aggregates and for reducing cellular vacuolization in HCT116 colon cancer cells and DU145 prostate cancer cells, thus mitigating endoplasmic reticulum stress and protecting against cell death. In contrast, autophagy induced by the same chemicals does not confer protection in a normal human colon cell line and in the non-transformed murine embryonic fibroblasts but rather contributes to cell death. Thus the impact of autophagy on cell survival during endoplasmic reticulum stress is likely contingent on the status of cells, which could be explored for tumor-specific therapy.

scholarly journals Signal transduction pathways that regulate cell survival and cell death

Oncogene ◽  
1998 ◽  
Vol 17 (25) ◽  
pp. 3207-3213 ◽  
Author(s):  
Tomislav Dragovich ◽  
Charles M Rudin ◽  
Craig B Thompson
Keyword(s):  
Signal Transduction ◽  
Cell Death ◽  
Cell Survival ◽  
Signal Transduction Pathways

scholarly journals PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Huiai Lu ◽  
Chunlei Mei ◽  
Luhao Yang ◽  
Junyan Zheng ◽  
Junwei Tong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Vitamin K ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Apoptotic Cell Death ◽  
Ampk Activation ◽  
Anticancer Activities ◽  
Bladder Cancer Cells

PPM-18, identified as a novel analog of vitamin K, has been reported to play a critical role in the suppression of seizures. However, the concerns that whether PPM-18, like vitamin K, exerts anticancer activity remain to be further investigated. Here, we found that PPM-18 remarkably suppressed the proliferation and induced apoptosis in bladder cancer cells. Furthermore, a significant autophagic effect of PPM-18 on bladder cancer cells was also demonstrated, which profoundly promoted apoptotic cell death. Mechanistically, PPM-18 activated AMP-activated protein kinase (AMPK), whereas it repressed PI3K/AKT and mTORC1 pathways in bladder cancer cells. Inhibition of AMPK markedly relieved PPM-18–induced autophagy and apoptosis, indicating that PPM-18 is able to induce autophagy and apoptosis in bladder cancer cells via AMPK activation. Moreover, reactive oxygen species (ROS) were notably accumulated in PPM-18–treated bladder cancer cells, and treatment with ROS scavengers not only eliminated ROS production but also abrogated AMPK activation, which eventually rescued bladder cancer cells from PPM-18–triggered autophagy and apoptotic cell death. In bladder cancer xenografts, the anticancer activities of PPM-18, including suppressing the growth of tumors and inducing autophagy and apoptosis in tumor cells, were also established. Collectively, this study was the first to demonstrate the anticancer effect of PPM-18 on bladder cancer cells in vitro and in vivo through eliciting autophagy and apoptosis via ROS and AMPK pathways, which might provide new insights into the potential utilization of PPM-18 for future bladder cancer treatment.

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