Activation of lysosomal mediated cell death in the course of autophagy by mTORC1 inhibitor

Khan, Sameer Ullah; Pathania, Anup Singh; Wani, Abubakar; Fatima, Kaneez; Mintoo, Mubashir J.; Hamza, Baseerat; Paddar, Masroor Ahmad; Wadhwa, Bhumika; Anand, Loveleena Kour; Maqbool, Mir Shahid; Mir, Sameer Ahmad; Kour, Jaspreet; Venkateswarlu, Vunnam; Mondhe, Dilip M.; Sawant, Sanghapal D.; Malik, Fayaz

doi:10.1038/s41598-022-07955-1

Cited by 9 publications

(7 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The above description provides us insights into how CSCs utilize the different processes and environmental factors to proliferate and survive under unfavorable conditions. Cell survival and cellular functions under nutrient deprivation, hypoxia, or in drug resistance, depend on an evolutionary conserved physiological process known as autophagy [53,[132][133][134]. Interestingly cancer and CSCs exploit this catabolic process to support tumorigenesis, maintain pluripotency, tumor progression, and relapse [135,136].…”

Section: Dysregulated Developmental Cues That Regulate Cscs Contribut...mentioning

confidence: 99%

Unveiling the mechanisms and challenges of cancer drug resistance

Khan,

Fatima,

Aisha

et al. 2024

Cell Commun Signal

Self Cite

View full text Add to dashboard Cite

Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer treatment strategies are evolving due to innate and acquired resistance capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells to survive and progress under unfavorable conditions. Although the mechanism of drug resistance is being widely studied to generate new target-based drugs with better potency than existing ones. However, due to the broader flexibility in acquired drug resistance, advanced therapeutic options with better efficacy need to be explored. Combination therapy is an alternative with a better success rate though the risk of amplified side effects is commonplace. Moreover, recent groundbreaking precision immune therapy is one of the ways to overcome drug resistance and has revolutionized anticancer therapy to a greater extent with the only limitation of being individual-specific and needs further attention. This review will focus on the challenges and strategies opted by cancer cells to withstand the current therapies at the molecular level and also highlights the emerging therapeutic options -like immunological, and stem cell-based options that may prove to have better potential to challenge the existing problem of therapy resistance.

show abstract

Section: Dysregulated Developmental Cues That Regulate Cscs Contribut...mentioning

confidence: 99%

Unveiling the mechanisms and challenges of cancer drug resistance

Khan,

Fatima,

Aisha

et al. 2024

Cell Commun Signal

Self Cite

View full text Add to dashboard Cite

show abstract

“…mTORC1 activates mitochondrial transcripts through 4E-BP1 and stimulates mitochondrial biogenesis by driving PGC1α (Summer et al, 2019). mTORC1 can simultaneously activate SREBPs, transcription factor ATF4, HIF1, Yin Yang 1 (YY1), PPARy, and PGC1a to drive mitochondrial regulation, ATP regulation, macromolecule synthesis, and cellular growth, blocking lysosomal biogenesis through transcription factor EB (TFEB) (Liu and Sabatini, 2020b;Zhu et al, 2022b;Khan et al, 2022;Cui et al, 2023). mTORC2 effectors include protein kinase B (Akt/PKB) and protein kinase C alpha (PKCα), which is a member of the AGC family of protein kinases (PKA/PKG/PKC).…”

Section: The Impact Of Modern Life On the Warburg Effect And Mitochon...mentioning

confidence: 99%

Mitochondria: It is all about energy

et al. 2023

View full text Add to dashboard Cite

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.

show abstract

“…Under normal and pathological circumstances, mTOR is implicated in the suppression of autophagy, which is otherwise triggered by nutrient stress and energy deprivation [ 99 , 100 ]. When autophagy is triggered, lysosomal degradation of cytosolic components occurs.…”

Section: Autophagy Apoptosis and Mtor Signalling: A Connecting Linkmentioning

confidence: 99%

Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer

et al. 2023

View full text Add to dashboard Cite

Mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cellular growth, development, survival, and metabolism through integration of diverse extracellular and intracellular stimuli. Additionally, mTOR is involved in interplay of signalling pathways that regulate apoptosis and autophagy. In cells, mTOR is assembled into two complexes, mTORC1 and mTORC2. While mTORC1 is regulated by energy consumption, protein intake, mechanical stimuli, and growth factors, mTORC2 is regulated by insulin-like growth factor-1 receptor (IGF-1R), and epidermal growth factor receptor (EGFR). mTOR signalling pathways are considered the hallmark in cancer due to their dysregulation in approximately 70% of cancers. Through downstream regulators, ribosomal protein S6 kinase β-1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), mTORC1 influences various anabolic and catabolic processes in the cell. In recent years, several mTOR inhibitors have been developed with the aim of treating different cancers. In this review, we will explore the current developments in the mTOR signalling pathway and its importance for being targeted by various inhibitors in anti-cancer therapeutics.

show abstract

Activation of lysosomal mediated cell death in the course of autophagy by mTORC1 inhibitor

Cited by 9 publications

References 44 publications

Unveiling the mechanisms and challenges of cancer drug resistance

Unveiling the mechanisms and challenges of cancer drug resistance

Mitochondria: It is all about energy

Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer

Contact Info

Product

Resources

About