scholarly journals CHCHD4 regulates a proliferation-EMT switch in tumour cells, through respiratory complex I mediated metabolism

2019 ◽  
Author(s):  
Luke W. Thomas ◽  
Cinzia Esposito ◽  
Jenna M. Stephen ◽  
Ana S. H. Costa ◽  
Christian Frezza ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Respiratory Chain ◽  
Tumour Cell ◽  
Complex I ◽  
Coiled Coil ◽  
Gene Signature ◽  
Tumour Cells ◽  
Mitochondrial Metabolism ◽  
Tumour Cell Proliferation

ABSTRACTBACKGROUNDMitochondrial metabolism involves oxidative phosphorylation (OXPHOS) via the respiratory chain and is required for the maintenance of tumour cell proliferation and regulation of epithelial–mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study we interrogate the role of CHCHD4-regulated respiratory chain activity and metabolism in tumour cell proliferation and EMT-related phenotypes.RESULTSWe show that CHCHD4 is essential for the proliferation of tumour cells irrespective of their aetiology. In human tumours, elevated CHCHD4 expression is correlated with a mitochondrial OXPHOS gene signature and with a proliferative gene signature associated with the mTORC1 signalling pathway. Elevated CHCHD4 increases tumour cell proliferation, in a manner that is dependent on complex I (CI) activity, glutamine consumption and mTORC1 activation. CHCHD4 expression is inversely correlated with EMT gene expression both in vitro and in vivo. Finally, we show CHCHD4 regulates the intracellular distribution of the EMT marker vimentin, in a CI-mediated manner.CONCLUSIONSCHCHD4 regulates tumour cell proliferation and metastatic (EMT-related) phenotypes through its control of CI-mediated mitochondrial metabolism.

scholarly journals Inhibitory effect of yoghurt and soya yoghurt containing bifidobacteria on the proliferation of Ehrlich ascites tumour cells in vitro and in vivo in a mouse tumour model

2004 ◽  
Vol 92 (1) ◽  
pp. 81-86 ◽  
Author(s):  
I. A. Abd El-Gawad ◽  
E. M. El-Sayed ◽  
S. A. Hafez ◽  
H. M. El-Zeini ◽  
F. A. Saleh
Keyword(s):  
Cell Proliferation ◽  
Tumour Cell ◽  
Tumour Cells ◽  
Soya Milk ◽  
Ascites Tumour ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Tumour ◽  
Tumour Cell Proliferation

The effect of yoghurt and soya yoghurt containing Bifidobacterium lactis Bb-12 or B. longum Bb-46 on Ehrlich ascites tumour cell proliferation was investigated in vitro and in vivo. Tumour cells were incubated with B. lactis Bb-12 or B. longum Bb-46 cultivated in de Mann Rogosa Sharpe (MRS) broth medium, or with their centrifuged supernatant fractions or sediments, for 2 h at 37°C. Treatment resulted in the inhibition of tumour cell proliferation by 85·42 (sd 0·78) and 85·10 (sd 1·28) % by intact micro-organisms, 77·61 (sd 0·29) and 71·43 (sd 1·75) % by their supernatant fractions, but only 4·00 (sd 0·19) and 9·09 (sd 1·24) % by the two sedimented bacteria, respectively. The incubation of tumour cells with yoghurt and soya yoghurt containing Bb-12 for 2 h resulted in 83·01 (sd 0·11) and 88·23 (sd 0·06) % inhibition, respectively, while it was 83·82 (sd 0·24) and 86·36 (sd 0·06) %, respectively for the same products containing Bb-46. Corresponding values for plain yoghurt and soya milk (without bifidobacteria) were 32·81 (sd 0·14) and 5·55 (sd 0·12) %, respectively. The differences between yoghurt or soya yoghurt containing Bb-12 or Bb-46 and plain yoghurt, soya milk or control treatments were statistically significant (n 3; P>0·05). Female Swiss albino mice were injected intraperitoneally with the same tumour cells. The lifespan of mice fed diets supplemented with yoghurt or soya yoghurt containing Bb-12 or Bb-46 was prolonged by 16, 23, 34 and 39%, respectively compared with that of the positive control group (n 6; P>0·05). The lifespan of groups fed plain yoghurt or soya milk was prolonged by 15 and 8%, respectively. Prolongation of lifespan was positively correlated with faeces bifidobacterial count in the groups fed yoghurt or soya yoghurt containing bifidobacteria (r 0·917; P>0·05).

scholarly journals In vivo tumour-cell proliferation after adriamycin treatment

1982 ◽  
Vol 45 (3) ◽  
pp. 429-437 ◽  
Author(s):  
R Rowley ◽  
H A Hopkins ◽  
W B Looney
Keyword(s):  
Cell Proliferation ◽  
Tumour Cell ◽  
Tumour Cell Proliferation

scholarly journals CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain

2019 ◽  
Author(s):  
Luke W. Thomas ◽  
Jenna M. Stephen ◽  
Cinzia Esposito ◽  
Simon Hoer ◽  
Robin Antrobus ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Complex I ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Tumour Progression ◽  
Coiled Coil ◽  
Mitochondrial Respiratory Chain ◽  
Tumour Cells ◽  
Stable Isotope Labelling ◽  
Mitochondrial Respiratory

ABSTRACTBACKGROUNDTumour cells rely on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to survive. Thus mitochondrial OXPHOS has become an increasingly attractive area for therapeutic exploitation in cancer. However, mitochondria are required for intracellular oxygenation and normal physiological processes, and it remains unclear which mitochondrial molecular mechanisms might provide therapeutic benefit. Previously, we discovered that coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) is critical for maintaining intracellular oxygenation and required for the cellular response to hypoxia (low oxygenation) in tumour cells through molecular mechanisms that we do not yet fully understand. Overexpression of CHCHD4 in human cancers, correlates with increased tumour progression and poor patient survival.RESULTSHere, we show that elevated CHCHD4 expression provides a proliferative and metabolic advantage to tumour cells in normoxia and hypoxia. Using stable isotope labelling with amino acids in cell culture (SILAC) and analysis of the whole mitochondrial proteome, we show that CHCHD4 dynamically affects the expression of a broad range of mitochondrial respiratory chain subunits from complex I-V, including multiple subunits of complex I (CI) required for complex assembly that are essential for cell survival. We found that loss of CHCHD4 protects tumour cells from respiratory chain inhibition at CI, while elevated CHCHD4 expression in tumour cells leads to significantly increased sensitivity to CI inhibition, in part through the production of mitochondrial reactive oxygen species (ROS).CONCLUSIONSOur study highlights an important role for CHCHD4 in regulating tumour cell metabolism, and reveals that CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain and CI biology.

scholarly journals MIP-2A Is a Novel Target of an Anilinoquinazoline Derivative for Inhibition of Tumour Cell Proliferation

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e76774 ◽  
Author(s):  
Mayuko Tokunaga ◽  
Hirokazu Shiheido ◽  
Noriko Tabata ◽  
Yuko Sakuma-Yonemura ◽  
Hideaki Takashima ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumour Cell ◽  
Tumour Cell Proliferation ◽  
Novel Target

Apoptosis, cell proliferation and in vivo biological behaviour of primary and metastatic tumour cells of an AKR lymphoma variant

APOPTOSIS ◽  
1997 ◽  
Vol 2 (2) ◽  
pp. 214-220 ◽  
Author(s):  
N. Donin ◽  
D. Katzenelson ◽  
J. Ravia ◽  
J. Hiss ◽  
G. Schiby ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumour Cells ◽  
Metastatic Tumour ◽  
Biological Behaviour

Tumour cell proliferation is abolished by inhibitors of and exchange

1993 ◽  
Vol 29 (1) ◽  
pp. 132-137 ◽  
Author(s):  
Branka Horvat ◽  
Shahram Taheri ◽  
Aida Salihagić
Keyword(s):  
Cell Proliferation ◽  
Tumour Cell ◽  
Tumour Cell Proliferation
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