Mitochondrial chaperone, TRAP1 modulates mitochondrial dynamics and promotes tumor metastasis

Dharaskar, Shrikant Purushottam; Paithankar, Khanderao; Vijayavittal, Abhijnya Kanugovi; Kara, Hatim Shabbir; Subbarao, Sreedhar Amere

doi:10.1016/j.mito.2020.08.001

Cited by 22 publications

(17 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRAP1 regulates the cell cycle to modulate cell proliferation (12) and promotes tumor metastasis by inducing mitochondrial fission (13). Furthermore, interference with the function of TRAP1 may result in the death of tumor cells but does not affect normal cells (13). Thus, an approach that selectively targets TRAP1 might be a promising strategy for the development of novel antitumor drugs.…”

Section: Introductionmentioning

confidence: 99%

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

et al. 2021

View full text Add to dashboard Cite

Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the heat shock protein 90 (Hsp90) chaperone family, protects cells against oxidative stress and maintains mitochondrial integrity. To date, numerous studies have focused on understanding the relationship between aberrant TRAP1 expression and tumorigenesis. Mitochondrial TRAP1 is a key regulatory factor involved in metabolic reprogramming in tumor cells that favors the metabolic switch of tumor cells toward the Warburg phenotype. In addition, TRAP1 is involved in dual regulation of the mitochondrial apoptotic pathway and exerts an antiapoptotic effect on tumor cells. Furthermore, TRAP1 is involved in many cellular pathways by disrupting the cell cycle, increasing cell motility, and promoting tumor cell invasion and metastasis. Thus, TRAP1 is a very important therapeutic target, and treatment with TRAP1 inhibitors combined with chemotherapeutic agents may become a new therapeutic strategy for cancer. This review discusses the molecular mechanisms by which TRAP1 regulates tumor progression, considers its role in apoptosis, and summarizes recent advances in the development of selective, targeted TRAP1 and Hsp90 inhibitors.

show abstract

Section: Introductionmentioning

confidence: 99%

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…For example, the current literature shows some conflicting results regarding the effects of inducing or downregulating TRAP1. One study found that cells overexpressing TRAP1 had enhanced proliferative potential compared to TRAP1 knockdown cells, along with increased tumor metastasis in vivo [127]. However, other studies found that the TRAP1 downregulation of SRC prevents cell invasiveness, as TRAP1 suppression enhanced cell invasiveness, and that TRAP1 levels were inversely related to the expression of genes associated with metastatic potential [126,174].…”

Section: Discussionmentioning

confidence: 99%

“…TRAP1 knockout cells displayed increased oxygen consumption, decreased glycolytic metabolites, increased citric acid cycle metabolites, and increased ROS [126,127]. TRAP1 overexpression was associated with mitochondrial fission, while TRAP1 knockdown cells displayed a more fused mitochondrial morphology [127].…”

Section: Trap1-stabilizing Mitochondrial Proteins and Inhibiting Oxidative Phosphorylationmentioning

confidence: 99%

“…Its regulatory roles in mitochondria include shifting metabolism towards glycolysis, contributing to mitochondrial stability, and combating oxidative stress by lowering ROS [41,[123][124][125]. TRAP1 knockout cells displayed increased oxygen consumption, decreased glycolytic metabolites, increased citric acid cycle metabolites, and increased ROS [126,127]. TRAP1 overexpression was associated with mitochondrial fission, while TRAP1 knockdown cells displayed a more fused mitochondrial morphology [127].…”

Section: Trap1-stabilizing Mitochondrial Proteins and Inhibiting Oxidative Phosphorylationmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial Metabolism in Melanoma

Huang

Radi

Arbiser

2021

Cells

View full text Add to dashboard Cite

Melanoma and its associated alterations in cellular pathways have been growing areas of interest in research, especially as specific biological pathways are being elucidated. Some of these alterations include changes in the mitochondrial metabolism in melanoma. Many mitochondrial metabolic changes lead to differences in the survivability of cancer cells and confer resistance to targeted therapies. While extensive work has gone into characterizing mechanisms of resistance, the role of mitochondrial adaptation as a mode of resistance is not completely understood. In this review, we wish to explore mitochondrial metabolism in melanoma and how it impacts modes of resistance. There are several genes that play a major role in melanoma mitochondrial metabolism which require a full understanding to optimally target melanoma. These include BRAF, CRAF, SOX2, MCL1, TRAP1, RHOA, SRF, SIRT3, PTEN, and AKT1. We will be discussing the role of these genes in melanoma in greater detail. An enhanced understanding of mitochondrial metabolism and these modes of resistance may result in novel combinatorial and sequential therapies that may lead to greater therapeutic benefit.

show abstract

“…TRAP1 expression is higher in tumour tissues compared to surrounding non-malignant tissues, and elevation of TRAP1 protein levels and gene copy number correlate with malignant progression and metastasis of colorectal carcinoma [ 70 , 71 , 72 ]. TRAP1 is also known to affect mitochondrial architecture and dynamics, where TRAP1 knockdown favours mitochondrial fusion, while TRAP1 overexpression induces mitochondrial fission and subsequently enhanced migration in vitro and in tumour metastasis in vivo [ 73 ].…”

Section: Associated Mitochondrial Mutations and Dysfunctionsmentioning

confidence: 99%

The Role of Mitochondria Dysfunction in Inflammatory Bowel Diseases and Colorectal Cancer

Kłos

Dabravolski

2021

IJMS

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is one of the leading gut chronic inflammation disorders, especially prevalent in Western countries. Recent research suggests that mitochondria play a crucial role in IBD development and progression to the more severe disease—colorectal cancer (CRC). In this review, we focus on the role of mitochondrial mutations and dysfunctions in IBD and CRC. In addition, main mitochondria-related molecular pathways involved in IBD to CRC transition are discussed. Additionally, recent publications dedicated to mitochondria-targeted therapeutic approaches to cure IBD and prevent CRC progression are discussed.

show abstract

Mitochondrial chaperone, TRAP1 modulates mitochondrial dynamics and promotes tumor metastasis

Cited by 22 publications

References 64 publications

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

Mitochondrial Metabolism in Melanoma

The Role of Mitochondria Dysfunction in Inflammatory Bowel Diseases and Colorectal Cancer

Contact Info

Product

Resources

About