Mitochondrial Respiratory Dysfunction Induces Claudin-1 Expression via Reactive Oxygen Species-mediated Heat Shock Factor 1 Activation, Leading to Hepatoma Cell Invasiveness

Lee, Jong-Hyuk; Lee, Young-Kyoung; Lim, Jin J.; Byun, Hae‐Ok; Park, Imkyong; Kim, Gyeong-Hyeon; Xu, Wei; Wang, Hee-Jung; Yoon, Gyesoon

doi:10.1074/jbc.m115.654913

Cited by 18 publications

(11 citation statements)

References 47 publications

(49 reference statements)

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“…For example, Ma et al ( 67 ) described that clones of breast cancer cells generated by treatment with rotenone, exhibited mitochondrial respiratory defects, increased ROS levels, and high migration and invasion properties, which were inhibited by treatment with antioxidants such as NAC and mito-TEMPO, a mitochondria-targeted antioxidant ( 67 ). Similar effects have also been observed in hepatoma cells ( 66 ). Altogether, these data suggest that the inhibition of Complex I activity accompanied by ROS generation promotes migration, invasion, and metastasis.…”

Section: Role Of Complex I In Metastasis Of Cancer Cellssupporting

confidence: 81%

“…As mutations in mtDNA represent an early event during breast tumorigenesis, producing defective OXPHOS with a metabolic shift toward glycolysis could be used as a potential biomarker for early detection and prognosis ( 65 ). In further support, several reports indicate that the inhibition of Complex I activity by pharmacologic interventions using small molecules can increase ROS generation, promoting the migration and invasion of cancer cells ( 62 , 66 , 67 ). For example, Ma et al ( 67 ) described that clones of breast cancer cells generated by treatment with rotenone, exhibited mitochondrial respiratory defects, increased ROS levels, and high migration and invasion properties, which were inhibited by treatment with antioxidants such as NAC and mito-TEMPO, a mitochondria-targeted antioxidant ( 67 ).…”

Section: Role Of Complex I In Metastasis Of Cancer Cellsmentioning

confidence: 71%

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The Mitochondrial Complex(I)ty of Cancer

Urra

Muñoz

Lovy³

et al. 2017

Front. Oncol.

126

115

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Recent evidence highlights that the cancer cell energy requirements vary greatly from normal cells and that cancer cells exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation. NADH–ubiquinone oxidoreductase (Complex I) is the largest complex of the mitochondrial electron transport chain and contributes about 40% of the proton motive force required for mitochondrial ATP synthesis. In addition, Complex I plays an essential role in biosynthesis and redox control during proliferation, resistance to cell death, and metastasis of cancer cells. Although knowledge about the structure and assembly of Complex I is increasing, information about the role of Complex I subunits in tumorigenesis is scarce and contradictory. Several small molecule inhibitors of Complex I have been described as selective anticancer agents; however, pharmacologic and genetic interventions on Complex I have also shown pro-tumorigenic actions, involving different cellular signaling. Here, we discuss the role of Complex I in tumorigenesis, focusing on the specific participation of Complex I subunits in proliferation and metastasis of cancer cells.

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Section: Role Of Complex I In Metastasis Of Cancer Cellssupporting

confidence: 81%

Section: Role Of Complex I In Metastasis Of Cancer Cellsmentioning

confidence: 71%

The Mitochondrial Complex(I)ty of Cancer

Urra

Muñoz

Lovy³

et al. 2017

Front. Oncol.

126

115

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“…However, from our knowledge, no evidence has been previously reported after Amph exposure regarding sensitized oxidative/inflammatory responses in brain microvessels. Furthermore, there is an established link between elevated ROS levels and further stimulating HSP70 synthesis as a protective response to apoptotic signaling (Horowitz & Robinson, ; Lee et al, ). Additionally, we found no sensitized response to the Amph challenge in brain microvessels obtained from animals pretreated with AT 1 ‐R blocker.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Marchese

Occhieppo

Basmadjian

et al. 2019

Eur J of Neuroscience

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Amphetamine‐induced neuroadaptations involve vascular damage, neuroinflammation, a hypo‐functioning prefrontal cortex (PFC), and cognitive alterations. Brain angiotensin II, through angiotensin type 1 receptor (AT1‐R), mediates oxidative/inflammatory responses, promoting endothelial dysfunction, neuronal oxidative damage and glial reactivity. The present work aims to unmask the role of AT1‐R in the development of amphetamine‐induced changes over glial and vascular components within PFC and hippocampus. Attention deficit was evaluated as a behavioral neuroadaptation induced by amphetamine. Brain microvessels were isolated to further evaluate vascular alterations after amphetamine exposure. Male Wistar rats were administered with AT1‐R antagonist, candesartan, followed by repeated amphetamine. After one week drug‐off period, animals received a saline or amphetamine challenge and were evaluated in behavioral tests. Afterward, their brains were processed for cresyl violet staining, CD11b (microglia marker), GFAP (astrocyte marker) or von Willebrand factor (vascular marker) immunohistochemistry, and oxidative/cellular stress determinations in brain microvessels. Statistical analysis was performed by using factorial ANOVA followed by Bonferroni or Tukey tests. Repeated amphetamine administration increased astroglial and microglial markers immunoreactivity, increased apoptotic cells, and promoted vascular network rearrangement at the PFC concomitantly with an attention deficit. Although the amphetamine challenge improved the attentional performance, it triggers detrimental effects probably because of the exacerbated malondialdehyde levels and increased heat shock protein 70 expression in microvessels. All observed amphetamine‐induced alterations were prevented by the AT1‐R blockade. Our results support the AT1‐R involvement in the development of oxidative/inflammatory conditions triggered by amphetamine exposure, affecting cortical areas and increasing vascular susceptibility to future challenges.

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“…For instance, HSF1 has been shown to upregulate β-catenin via HuR [63] and loss of HSF1 reduced NFκB activation and suppressed tumor growth [16]. HSF1 activation in hepatoma cells led to HSF1-driven Cln-1 expression leading to cell invasion [64]. Loss of HSF1 in a lung tumor model also showed a decrease in migration associated with a decrease in vinculin, an actin-binding protein known to promote cell migration [60].…”

Section: Role Of Hsf1 In Tumor Progressionmentioning

confidence: 99%

HSF1 as a Cancer Biomarker and Therapeutic Target

Carpenter

Gökmen–Polar

2019

CCDT

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Heat shock factor 1 (HSF1) was discovered in 1984 as the master regulator of the heat shock response. In this classical role, HSF1 is activated following cellular stresses such as heat shock that ultimately lead to HSF1-mediated expression of heat shock proteins to protect the proteome and survive these acute stresses. However, it is now becoming clear that HSF1 also plays a significant role in several diseases, perhaps none more prominent than cancer. HSF1 appears to have a pleiotropic role in cancer by supporting multiple facets of malignancy including migration’ invasion, proliferation, and cancer cell metabolism among others. Because of these functions, and others, of HSF1, it has been investigated as a biomarker for patient outcomes in multiple cancer types. HSF1 expression alone was predictive for patient outcomes in multiple cancer types but in other instances, markers for HSF1 activity were more predictive. Clearly, further work is needed to tease out which markers are most representative of the tumor promoting effects of HSF1. Additionally, there have been several attempts at developing small molecule inhibitors to reduce HSF1 activity. All of these HSF1 inhibitors are still in preclinical models but have shown varying levels of efficacy at suppressing tumor growth. The growth of research related to HSF1 in cancer has been enormous over the last decade with many new functions of HSF1 discovered along the way. In order for these discoveries to reach clinical impact, further development of HSF1 as a biomarker or therapeutic target needs to be continued.

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Mitochondrial Respiratory Dysfunction Induces Claudin-1 Expression via Reactive Oxygen Species-mediated Heat Shock Factor 1 Activation, Leading to Hepatoma Cell Invasiveness

Cited by 18 publications

References 47 publications

The Mitochondrial Complex(I)ty of Cancer

The Mitochondrial Complex(I)ty of Cancer

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

HSF1 as a Cancer Biomarker and Therapeutic Target

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