Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis

Rademaker, Gilles; Costanza, Brunella; Bellier, Justine; Herfs, Michaël; Peiffer, Raphaël; Agirman, Ferman; Maloujahmoum, Naïma; Habraken, Yvette; Delvenne, Philippe; Bellahcène, Akeila; Castronovo, Vincenzo; Peulen, Olivier

doi:10.1038/s41389-019-0130-6

Cited by 23 publications

(33 citation statements)

References 56 publications

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“…Myoferlin is required for high oxidative phosphorylation activity and maintenance of an organized mitochondrial network. 38 In addition, Rademaker et al 38…”

Section: Myoferlin In Colon Cancermentioning

confidence: 99%

“…But cancer cells with more flexible metabolic phenotype have stronger resistance. In triple‐negative breast cancer, PDAC and colon cancer cells, myoferlin was described as an essential molecule to maintain a high oxidative phosphorylation activity. The mechanism will be discussed in the next section.…”

Section: Roles Of Myoferlin In Cancersmentioning

confidence: 99%

“…In addition, overexpression of myoferlin often indicates a poor prognosis. Specifically, myoferlin is an independent prognostic factor in pancreatic adenocarcinoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma patients, clear cell renal cell carcinoma, colon cancer and non‐small‐cell lung carcinoma patients.…”

Section: Roles Of Myoferlin In Cancersmentioning

confidence: 99%

“…Myoferlin is required for high oxidative phosphorylation activity and maintenance of an organized mitochondrial network . In addition, Rademaker et al also found that myoferlin silencing causes reactive oxygen species (ROS) accumulation, p53‐dependent reduction of cell growth, enhanced DNA damage response and increased apoptosis. These authors revealed that myoferlin could represent a suitable target for new anticancer therapies.…”

Section: Roles Of Myoferlin In Cancersmentioning

confidence: 99%

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Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers

Zhu

Zhou

Zhao

et al. 2019

J Cellular Molecular Medi

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Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non‐small‐cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which mainly included promoting angiogenesis, vasculogenic mimicry, energy metabolism reprogramming, epithelial‐mesenchymal transition and modulating exosomes. The roles of myoferlin in both normal cells and cancer cells are of great significance to provide novel and efficient methods of tumour treatment. In this review, we summarize recent studies and findings of myoferlin and suggest that myoferlin is a novel potential candidate for clinical diagnosis and targeted cancer therapy.

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“…Myoferlin is required for high oxidative phosphorylation activity and maintenance of an organized mitochondrial network. 38 In addition, Rademaker et al 38…”

Section: Myoferlin In Colon Cancermentioning

confidence: 99%

Section: Roles Of Myoferlin In Cancersmentioning

confidence: 99%

Section: Roles Of Myoferlin In Cancersmentioning

confidence: 99%

Section: Roles Of Myoferlin In Cancersmentioning

confidence: 99%

See 2 more Smart Citations

Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers

Zhu

Zhou

Zhao

et al. 2019

J Cellular Molecular Medi

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“…Mitochondria and NADPH oxidase (NOX) were the major sources of ROS [19]; in the present study, the decrease in mitochondrial membrane potential and increase in NOX2 expression of ECs under stretch were reported (Figures 2(b) and 2(c)); after pretreatment with gp91ds-tat or MitoTEMPO, the level of ROS was decreased (Figure 2(a)), which suggested that ROS might originate from the mitochondria and NOX2 of ECs treated by stretch. As the chief source of free radicals, ROS participates in cell damage and apoptosis [29]; in this study, NAC pretreatment not only reduced the level of ROS but also mitigated the apoptosis of ECs under stretch.…”

mentioning

confidence: 56%

Simvastatin Mitigates Apoptosis and Transforming Growth Factor-Beta Upregulation in Stretch-Induced Endothelial Cells

Dong

Huang

Jiang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Portal hypertension is a common clinical symptom of digestive disorders. With an increase in portal pressure, the portal vein will continue to dilate. We aimed to determine whether continuous stretch induced by portal hypertension may impair the function of endothelial cells (ECs) in the portal vein and aggravate the progress of portal hypertension and explore its mechanism. ECs were cultured on an elastic silicone membrane and subjected to continuous uniaxial stretch. Apoptosis and expression of TGF-β in ECs under stretch were measured. We found that sustained stretch induced the apoptosis of ECs in a stretch length-dependent manner. Compared with the control, continuous stretch increased the nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression and damaged the mitochondria, resulting in an evident increase in reactive oxygen species (ROS) levels; pretreatment with gp91ds-tat or MitoTEMPO decreased the ROS level in the intracellular levels. N-acetyl-cysteine (NAC) treatment before stretch not only reduced ROS levels but also mitigated the apoptosis of ECs; simvastatin had similar effects through targeting NOX2 and mitochondria. During the stretch, the phosphorylation of p38 mitogen-activated protein kinase (P38MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB) was obviously increased; pretreatment with P38MAPK or JNK inhibitors decreased the phosphorylation of NF-κB and TGF-β expression. Pyrrolidine dithiocarbamate (PDTC) treatment before stretch also reduced TGF-β expression. After pretreatment with NAC, the phosphorylation of P38MAPK, JNK, and NF-κB and TGF-β expressions in ECs under stretch was suppressed; similar results were observed in simvastatin-treated ECs. This study demonstrated that simvastatin could mitigate EC apoptosis and TGF-β upregulation induced by continuous stretch by reducing the level of ROS.

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A potent and selective small molecule inhibitor of myoferlin attenuates colorectal cancer progression

Kan

et al. 2021

Clinical & Translational Med

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As a pivotal vesicular trafficking protein, Myoferlin (MYOF) has become an attractive target for cancer therapy. However, the roles of MYOF in colorectal cancer invasion remain enigmatic, and MYOF‐targeted therapy in this malignancy has not been explored. In the present study, we provided the first functional evidence that MYOF promoted the cell invasion of colorectal cancer. Furthermore, we identified a novel small molecule inhibitor of MYOF (named YQ456) that showed high binding affinity to MYOF (KD = 37 nM) and excellent anti‐invasion capability (IC50 = 110 nM). YQ456 was reported for the first time to interfere with the interactions between MYOF and Ras‐associated binding (Rab) proteins at low nanomolar levels. This interference disrupted several vesicle trafficking processes, including lysosomal degradation, exosome secretion, and mitochondrial dynamics. Further, YQ456 exhibited excellent inhibitory effects on the growth and invasiveness of colorectal cancer. As the first attempt, the anticancer efficacy of YQ456 in the patient‐derived xenograft (PDX) mouse model indicated that targeting MYOF may serve as a novel and practical therapeutic approach for colorectal cancer.

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Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis

Cited by 23 publications

References 56 publications

Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers

Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers

Simvastatin Mitigates Apoptosis and Transforming Growth Factor-Beta Upregulation in Stretch-Induced Endothelial Cells

A potent and selective small molecule inhibitor of myoferlin attenuates colorectal cancer progression

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