Clusterin as modulator of carcinogenesis: A potential avenue for targeted cancer therapy

Praharaj, Prakash Priyadarshi; Patra, Srimanta; Panigrahi, Debasna Pritimanjari; Patra, Samir Kumar; Bhutia, Sujit K.

doi:10.1016/j.bbcan.2020.188500

Cited by 29 publications

(35 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[13,14,[32][33][34][35][36][37] Clusterin has been proposed to interact with client proteins via an as yet undefined ''molten globule''-like domain(s). [38] In addition to its chaperone capacity, Clusterin functions in sperm maturation, [39] cell differentiation, [40] regulation of cell death and survival mechanisms, [41] and as an anti-inflammatory inhibitor of the complement system. [42,43] Moreover, it is often overlooked that Clusterin is an apolipoprotein (ApoJ) that has been identified in plasma high-density lipoprotein particles, suggesting a role in lipid and cholesterol metabolism.…”

Section: Clusterin An Unusual Chaperonementioning

confidence: 99%

“…[46,47] While Clusterin is mainly located in the extracellular space, several reports described the presence of intracellular Clusterin (iClu) under specific stress conditions. [34,41,[48][49][50] An increase in iClu levels has been observed in neurons upon exposure to Aβ oligomers and has been suggested to play a role in mediating Aβ toxicity. [51] The biogenesis and regulation of iClu has mainly been studied in certain cancer cells where it is abundant, [41] but its biogenesis is not well understood.…”

Section: Clusterin An Unusual Chaperonementioning

confidence: 99%

“…[34,41,[48][49][50] An increase in iClu levels has been observed in neurons upon exposure to Aβ oligomers and has been suggested to play a role in mediating Aβ toxicity. [51] The biogenesis and regulation of iClu has mainly been studied in certain cancer cells where it is abundant, [41] but its biogenesis is not well understood. Although alternative splicing and alternative initiation codons have been implicated, the mRNA species for these Clusterin isoforms are of very low abundance.…”

Section: Clusterin An Unusual Chaperonementioning

confidence: 99%

See 2 more Smart Citations

The chaperone Clusterin in neurodegeneration−friend or foe?

Yuste-Checa

Bracher

2022

BioEssays

View full text Add to dashboard Cite

Fibrillar protein aggregates are the pathological hallmark of a group of age-dependent neurodegenerative conditions, including Alzheimer's and Parkinson's disease. Aggregates of the microtubule-associated protein Tau are observed in Alzheimer's disease and primary tauopathies. Tau pathology propagates from cell to cell in a prion-like process that is likely subject to modulation by extracellular chaperones such as Clusterin. We recently reported that Clusterin delayed Tau fibril formation but enhanced the activity of Tau oligomers to seed aggregation of endogenous Tau in a cellular model. In contrast, Clusterin inhibited the propagation of α-Synuclein aggregates associated with Parkinson's disease. These findings raise the possibility of a mechanistic link between Clusterin upregulation observed in Alzheimer's disease and the progression of Tau pathology. Here we review the diverse functions of Clusterin in the pathogenesis of neurodegenerative diseases, focusing on evidence that Clusterin may act either as a suppressor or enhancer of pathology.

show abstract

Section: Clusterin An Unusual Chaperonementioning

confidence: 99%

Section: Clusterin An Unusual Chaperonementioning

confidence: 99%

Section: Clusterin An Unusual Chaperonementioning

confidence: 99%

See 1 more Smart Citation

The chaperone Clusterin in neurodegeneration−friend or foe?

Yuste-Checa

Bracher

2022

BioEssays

View full text Add to dashboard Cite

show abstract

“…In another study, ERK1‐mediated activation of DRP1 is important for modulating mitochondrial fission, which favours mesenchymal stem cell (MSC)‐triggered drug resistance in T‐cell acute lymphoblastic leukaemia (T‐ALL) cells and protects them from chemotherapeutic drugs (Cai et al, 2016). Altering mitochondrial dynamics through selective inhibition of clusterin (molecular chaperone) also increased drug sensitivity towards camptothecin in breast CSCs, causing necrosis (Arumugam et al, 2017; Praharaj et al, 2020). Therefore, mitochondrial fission in CSCs would be a more potent target for the selective eradication of CSCs (Figure 2).…”

Section: Modulation Of Mitochondrial Dynamics In Cscs: a Necessary Pr...mentioning

confidence: 99%

Dysregulation of mitophagy and mitochondrial homeostasis in cancer stem cells: Novel mechanism for anti‐cancer stem cell‐targeted cancer therapy

Praharaj

Patro

Bhutia

2021

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Despite the potential of cancer medicine, cancer stem cells (CSCs) associated with chemoresistance and disease recurrence are the significant challenges currently opposing the efficacy of available cancer treatment options. Mitochondrial dynamics involving the fission–fusion cycle and mitophagy are the major contributing factors to better adaptation, enabling CSCs to survive and grow better under tumour micro‐environment‐associated stress. Moreover, mitophagy is balanced with mitochondrial biogenesis to maintain mitochondrial homeostasis in CSCs, which are necessary for the growth and maintenance of CSCs and regulate metabolic switching from glycolysis to oxidative phosphorylation. In this review, we discuss different aspects of mitochondrial dynamics, mitophagy, and mitochondrial homeostasis and their effects on modulating CSCs behaviour during cancer development. Moreover, the efficacy of pharmacological targeting of these cellular processes using anti‐CSC drugs in combination with currently available chemotherapeutic drugs improves the patient's survival of aggressive cancer types.

show abstract

“… 12 Besides, recent studies have revealed that CLU is upregulated in most stressed conditions and related to numerous tumor-associated signaling networks, such as epithelial-mesenchymal transition (EMT), metastasis, tumor progression, therapy resistance, and programmed cell death. 13 On the contrary, there were also some studies showing that the expression of CLU in tumors of different genetic origins is lower than in corresponding normal tissues. 14 , 15 In non-small cell lung cancer, CLU was found to be less expressed in tumor tissues than in normal tissues.…”

Section: Introductionmentioning

confidence: 99%