HSP40 Interacts with Pyruvate Kinase M2 and Regulates Glycolysis and Cell Proliferation in Tumor Cells

Huang, Liangqian; Yu, Zhenhai; Zhang, Teng; Zhao, Xiaoping; Huang, Gang

doi:10.1371/journal.pone.0092949

Cited by 30 publications

(24 citation statements)

References 34 publications

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“…PDK1 overexpression in Wnt-inhibited cancer cells rescues glycolysis and vessel growth. Heat shock proteins (HSPs) including HSP40 [53] and TNF receptor-associated protein 1 (TRAP1) [86], a member of the HSP90 chaperone family, are involved in the regulation of metabolic switch between OXPHOS and aerobic glycolysis in tumors. Focal adhesion kinase (FAK), a key transmitter of growth factor and anchorage stimulation, enhances glycolysis and decreases mitochondrial respiration through the upregulation of glycolytic proteins enolase, PKM2, LDH and MCT [45].…”

Section: Regulation Of Glycolysis In Tumorsmentioning

confidence: 99%

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

Chen

Wang

et al. 2016

Oncotarget

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Metabolic change is one of the hallmarks of tumor, which has recently attracted a great of attention. One of main metabolic characteristics of tumor cells is the high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in glycolysis pathway than that in tricarboxylic acid cycle. The molecular mechanism of a high glycolytic flux in tumor cells remains unclear. A large amount of intermediates derived from glycolytic pathway could meet the biosynthetic requirements of the proliferating cells. Hypoxia-induced HIF-1α, PI3K-Akt-mTOR signaling pathway, and many other factors, such as oncogene activation and tumor suppressor inactivation, drive cancer cells to favor glycolysis over mitochondrial oxidation. Several small molecules targeting glycolytic pathway exhibit promising anticancer activity both in vitro and in vivo. In this review, we will focus on the latest progress in the regulation of aerobic glycolysis and discuss the potential targets for the tumor therapy.

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Section: Regulation Of Glycolysis In Tumorsmentioning

confidence: 99%

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

Chen

Wang

et al. 2016

Oncotarget

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“…Recently, HSPs have also been shown to target aerobic glycolysis and to suppress the growth of cancer cells. HSP40 binds to and destabilizes the pyruvate kinase muscle isozyme 2 (PKM2) isoform, which leads to the downregulation of PKM2-mediated PDK1 expression followed by cancer cell growth inhibition [54]. Mitochondrial HSPs, such as HSP70, protect mitochondria against damage from simulated ischemia and/or reperfusion that could occur as a result of decrease in ROS, leading to the preservation of mitochondrial complex activities and, hence, ATP formation [55].…”

Section: Hsp Regulation Of Mitochondria Functionmentioning

confidence: 99%

Restoration of mitochondria function as a target for cancer therapy

Bhat

Kumar

Chaudhary

et al. 2015

Drug Discovery Today

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Defective oxidative phosphorylation has a crucial role in the attenuation of mitochondrial function, which confers therapy resistance in cancer. Various factors, including endogenous heat shock proteins (HSPs) and exogenous agents such as dichloroacetate, restore respiratory and other physiological functions of mitochondria in cancer cells. Functional mitochondria might ultimately lead to the restoration of apoptosis in cancer cells that are refractory to current anticancer agents. Here, we summarize the key reasons contributing to mitochondria dysfunction in cancer cells and whether and/or how restoration of mitochondrial function could be exploited for cancer therapeutics.

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“…In a non-tumoral model of rat brain, D3 participates in the hypoxia-induced reduction in TH signaling. Moreover, ischemia/hypoxia induces a heatshock protein 40 (HSP40)-mediated translocation of D3 to the nucleus, facilitating TH inactivation proximal to the TH receptors (Jo et al 2012, Huang et al 2014. THs can directly protect or damage cells by modulating oxidative stress (Mancini et al 2016).…”

Section: Dysregulation Of Cell Bioenergetics/energy Metabolismmentioning

confidence: 99%

Role of thyroid hormones in the neoplastic process: an overview

Goemann¹,

Romitti²,

Meyer³

et al. 2017

Endocrine-Related Cancer

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Thyroid hormones (TH) are critical regulators of several physiological processes, which include development, differentiation and growth in virtually all tissues. In past decades, several studies have shown that changes in TH levels caused by thyroid dysfunction, disruption of deiodinases and/or thyroid hormone receptor (TR) expression in tumor cells, influence cell proliferation, differentiation, survival and invasion in a variety of neoplasms in a cell type-specific manner. The function of THs and TRs in neoplastic cell proliferation involves complex mechanisms that seem to be cell specific, exerting effects via genomic and nongenomic pathways, repressing or stimulating transcription factors, influencing angiogenesis and promoting invasiveness. Taken together, these observations indicate an important role of TH status in the pathogenesis and/or development of human neoplasia. Here, we aim to present an updated and comprehensive picture of the accumulated knowledge and the current understanding of the potential role of TH status on the different hallmarks of the neoplastic process.

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HSP40 Interacts with Pyruvate Kinase M2 and Regulates Glycolysis and Cell Proliferation in Tumor Cells

Cited by 30 publications

References 34 publications

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

Restoration of mitochondria function as a target for cancer therapy

Role of thyroid hormones in the neoplastic process: an overview

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