Engaging the Lysosome and Lysosome-Dependent Cell Death in Cancer

Berg, Anastasia L.; Rowson-Hodel, Ashley; Wheeler, Madelyn R.; Hu, Michelle; Free, Savannah R.; Carraway, Kermit L.

doi:10.36255/exon-publications-breast-cancer-lysosome

Cited by 10 publications

(12 citation statements)

References 340 publications

(425 reference statements)

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“…Depletion of cancer cells through LMP is an attractive therapeutic strategy, holding particular promise for combating apoptosis-resistant cancer cell populations. Several lysosome-disrupting agents (lysosomotropic agents, sphingolipids, nanoparticles) are currently under investigation or in clinical development for cancer and other indications 96 . Alkaliptosis, a pH-dependent form of RCD, has also been recently identified as a new strategy for cancer therapy across multiple tumor types.…”

Section: Types Of Regulated Cell Death and Application In Cancermentioning

confidence: 99%

Current evidence and therapeutic implication of PANoptosis in cancer

Ocansey,

Qian,

Cai

et al. 2024

Theranostics

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Regulated cell death (RCD) is considered a critical pathway in cancer therapy, contributing to eliminating cancer cells and influencing treatment outcomes. The application of RCD in cancer treatment is marked by its potential in targeted therapy and immunotherapy. As a type of RCD, PANoptosis has emerged as a unique form of programmed cell death (PCD) characterized by features of pyroptosis, apoptosis, and necroptosis but cannot be fully explained by any of these pathways alone. It is regulated by a multi-protein complex called the PANoptosome. As a relatively new concept first described in 2019, PANoptosis has been shown to play a role in many diseases, including cancer, infection, and inflammation. This study reviews the application of PCD in cancer, particularly the emergence and implication of PANoptosis in developing therapeutic strategies for cancer. Studies have shown that the characterization of PANoptosis patterns in cancer can predict survival and response to immunotherapy and chemotherapy, highlighting the potential for PANoptosis to be used as a therapeutic target in cancer treatment. It also plays a role in limiting the spread of cancer cells. PANoptosis allows for the elimination of cancer cells by multiple cell death pathways and has the potential to address various challenges in cancer treatment, including drug resistance and immune evasion. Moreover, active investigation of the mechanisms and potential therapeutic agents that can induce PANoptosis in cancer cells is likely to yield effective cancer treatments and improve patient outcomes. Research on PANoptosis is still ongoing, but it is a rapidly evolving field with the potential to lead to new treatments for various diseases, including cancer.

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Section: Types Of Regulated Cell Death and Application In Cancermentioning

confidence: 99%

Current evidence and therapeutic implication of PANoptosis in cancer

Ocansey,

Qian,

Cai

et al. 2024

Theranostics

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“…These degradative enzymes are mainly active at the low pH (4.8) of the lysosomal lumen, which is maintained by the activity of the lysosomal proton pump V-ATPase. The main function of lysosomes is the degradation of extracellular components consumed by endocytosis, phagocytosis, or intracellular contents obtained by autophagy [ 18 ]. Lysosomes are essential for tumor growth, invasion, and metastasis.…”

Section: Lysosomes In Cancermentioning

confidence: 99%

“…Additionally, the fusion of lysosomes with the plasma membrane allows V-ATPase to pump protons from lysosomes into the extracellular space, further promoting cancer invasion. Lastly, lysosomes also capture and exocytose hydrophobic and weakly basic chemotherapeutics, leading to drug resistance [ 3 , 18 ].…”

Section: Lysosomes In Cancermentioning

confidence: 99%

“…It is not surprising that cancer cells exhibit an increase in the number, volume, and enzyme content of lysosomes. Additionally, cancer cell lysosomes are more fragile compared to normal cells, due to their larger size and unique characteristics of the lysosomal membrane structure [ 18 ]. The membrane of cancer cell lysosomes has decreased concentrations of the stabilizing molecule lysosomal-associated membrane protein (LAMP) and increased concentrations of the lysosome-destabilizing lipid sphingosine.…”

Section: Lysosomes In Cancermentioning

confidence: 99%

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The Exploitation of Lysosomes in Cancer Therapy with Graphene-Based Nanomaterials

et al. 2023

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Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumulate in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets, suppressing their anticancer effects. A number of chemical modifications are made to GNMs to facilitate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable the lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabilization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective autophagy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable tumor cell identification and therapy monitoring. In this review, we explain how the characteristics of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited for GNM-based cancer therapy.

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“…The execution of Parthanatos does not depend on the mediation of caspases, but on the overactivation of ribozyme, PARP-1 [15; 16]. lysosomedependent cell death is hallmarked by lysosomal destabilization and dependence on lysosomal membrane permeabilization [17]. Autophagy is the process of transporting endogenous or exogenous cytoplasmic substances to lysosomes for recycling the basic components of cells through degradation .Autophagy-dependent cell death is considered to be a form of PCD that is mechanistically dependent on the autophagic machinery, independent of apoptosis or necrosis.…”

Section: Introductionmentioning

confidence: 99%

Leveraging diverse cell-death patterns to predict the prognosis, immunotherapy and drug sensitivity of clear cell renal cell carcinoma

Zhang

Song

Wang

et al. 2023

Preprint

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Background Programmed cell death (PCD) on the prognosis, tumor microenvironment characteristics and immunotherapy response of patients with clear cell renal cell carcinoma (ccRCC) have not been fully elucidated.Methods The PCD-related signature (PRS) was constructed using the least absolute shrinkage and selection operator regression (LASSO) method to evaluate the PCD characteristics of ccRCC. The E-MTAB-1980 dataset was used as an external validation set. PCD-related clusters were constructed using non-negative matrix factorization (NMF). The different algorithms were used for the investigation of the immune infiltration scores. The Cancer Immunome Atlas (TCIA) was used to download immunotherapy data for ccRCC. The Genomics of Drug Sensitivity in Cancer (GDSC) database was employed to analyze the differences in drug sensitivity of the models. Single cell sequencing data, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and qRT-PCR were used to check for differences in protein and mRNA expression of PRGs between cancerous and paracancerous tissue.Results PRS may be utilized to distinguish patients' prognosis, immune characteristics, tumor mutation burden, immunotherapy response, and drug sensitivity. Five genes were found to play crucial roles in the promotion of cancer and three genes in the suppression of cancer. qRT-PCR and CPTAC indicated that five genes were overexpressed and three genes were underexpressed in the ccRCC tissues.Conclusion Overall, by synthesising different cell death patterns, we have established a novel PCD model that can accurately predict the clinical prognosis, mutational and immune characteristics of ccRCC.

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Engaging the Lysosome and Lysosome-Dependent Cell Death in Cancer

Cited by 10 publications

References 340 publications

Current evidence and therapeutic implication of PANoptosis in cancer

Current evidence and therapeutic implication of PANoptosis in cancer

The Exploitation of Lysosomes in Cancer Therapy with Graphene-Based Nanomaterials

Leveraging diverse cell-death patterns to predict the prognosis, immunotherapy and drug sensitivity of clear cell renal cell carcinoma

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