Distinct functions of dynamin isoforms in tumorigenesis and their potential as therapeutic targets in cancer

Meng, Jianghui

doi:10.18632/oncotarget.16678

Cited by 23 publications

(26 citation statements)

References 112 publications

(128 reference statements)

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“…DNM2 has been implicated as a therapeutic target for cervical cancer: In Hela cells, dynamin-2 inhibitors have been demonstrated to cause decreased migration and invasion via decreasing the expression of matrix metallopeptidase 9, thereby lowering the rate of cell proliferation (57). Similar to Cav-1, an increase in the expression of DNM2 has been demonstrated to correspond to advances in the tumor stage (19). In the present study, the expression levels of DNM2 and Cav-1 genes exhibited a marked correlation with the progression of bladder tumor stage.…”

Section: Discussionsupporting

confidence: 69%

“…Similarly, together with Cav-1, DNM2 also mediates effects on cancer formation and progression. The 2 proteins are involved in the endocytosis of a number of receptor proteins, ligands and signaling molecules (19,62). However, it has been suggested that there are several other interlinked signaling pathways that, in response to overexpression of Cav-1 and DNM2, may be activated and/or deactivated, resulting in tumor formation (63).…”

Section: Discussionmentioning

confidence: 99%

“…Dynamin-2 protein dysfunction results in the dysregulation of endosome recycling, causing an imbalanced expression of regulatory growth factor receptors, including epidermal growth factor receptor, on the cell surface, promoting aberrant cell growth, invasion and proliferation (15). Overexpression of Cav-1 and DNM2 has been demonstrated to be involved in cell lines of various types of cancer, including pancreatic, colon, lung, breast and prostate cancer (13,(16)(17)(18)(19)(20)(21)(22).…”

Section: Caveolin-1 and Dynamin-2 Overexpression Is Associated With Tmentioning

confidence: 99%

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Caveolin‑1 and dynamin‑2 overexpression is associated with the progression of bladder cancer

et al. 2019

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Caveolae-mediated endocytosis regulates cell adhesion and growth in an anchorage-dependent manner. Studies of the endocytic function of caveolae have suggested a wide-ranging list of cargoes, including a number of receptors and extracellular proteins, ligands and nutrients from the extracellular matrix. Disruption of the processes of caveolae-mediated endocytosis mediated by signaling proteins is critical to cellular integrity. Caveolin-1 and dynamin-2 are the 2 major proteins associated with endocytotic function. Mechanistically, dynamin-2 has a co-equal role with caveolin-1 in terms of caveolae-derived endosome formation. Recent studies have revealed the pathological outcomes associated with the dysregulation of caveolin-1 and dynamin-2 expression. Increased expression levels of the gene for caveolin, Cav-1, resulting in augmented cellular metastasis and invasion, have been demonstrated in various types of cancer, and overexpression of the gene for dynamin-2, DNM2, has been associated with tumorigenesis in cervical, pancreatic and lung cancer. An increased expression of Cav-1 and DNM2 is known to be associated with the invasive behavior of cancer cells, and with cancer progression. Furthermore, it has been previously demonstrated that, in caveolar assembly and caveolae mediated endocytosis, Cav-1 interacts directly with DNM2 during the processes. Altered expression of the 2 genes is critical for the normal function of the cell. The expression patterns of Cav-1 and DNM2 have been previously examined in bladder cancer cell lines, and were each demonstrated to be overexpressed. In the present study, the expression levels of these 2 genes in bladder cancer samples were quantified. The gene expression levels of Cav-1 and DNM2 were identified to be increased 8.88-and 8.62-fold, respectively, in tumors compared with the normal controls. Furthermore, high-grade tumors exhibited significantly increased expression levels of Cav-1 and DNM2 (both P<0.0001) compared with the low-grade tumors. In addition, compared with normal control samples, the expression of the 2 genes in tumor samples was observed to be highly significant (P<0.0001), with a marked positive correlation identified for the tumors (Pearson's correlation coefficient, r=0.80 for the tumor samples vs. r=0.32 in the normal control samples). Taken together, the results of the present study demonstrated that the overexpression of Cav-1 and DNM2 genes, and a determination of their correlation coefficients, may be a potential risk factor for bladder cancer, in addition to other clinical factors.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Caveolin-1 and Dynamin-2 Overexpression Is Associated With Tmentioning

confidence: 99%

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Caveolin‑1 and dynamin‑2 overexpression is associated with the progression of bladder cancer

et al. 2019

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“…Functional studies suggest that dynamin proteins can participate in promoting cell migration and metastasis in PDAC cellular and mouse models (43,44). In addition, in a recent study, dynamins and their complexes have been hypothesized as important therapeutic targets in cancer (45). The association between aggressiveness of cancers and expression of dynamins and their protein complexes is well matched with our data, where the alleles associated with decreased survival are associated with an increase in DNMBP gene expression, as shown in GTEx.…”

Section: Discussionsupporting

confidence: 89%

Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients

et al. 2019

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Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, caused by various factors, such as the aggressiveness of the disease, the limited therapeutic options and the lack of early detection and risk markers. The ATP binding cassette subfamily C member 2 (ABCC2) protein plays a critical role in response to various drugs and is differentially expressed in gemcitabine sensitive and resistant cells. Moreover, Single Nucleotide Polymorphisms (SNPs) in the gene have been associated with differential outcomes and prognosis in several tumour types. The aim of this study was to investigate the possible

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“…The present findings show that a HFA diet induces differential changes in the mammary gland transcriptome, with Dynamin 1 ( Dnm1 ) the top upregulated gene, and Bcl-2-binding component 3 ( Bbc3) the top downregulated gene. Dnm1 plays an essential role in endocytosis and is upregulated in many cancers where it has been suggested to attenuate apoptotic signalling [ 39 ], while Bbc3 which encodes the p53 upregulated modulator of apoptosis (PUMA) is downregulated in some cancers. PUMA is a target of the tumour suppressor protein p53 and is necessary for stress-induced apoptosis [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice

et al. 2020

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Folic acid (FA) intake has been associated with increased breast cancer risk in some studies. Although underlying mechanisms are unknown, epigenetic modifications that persistently alter transcription have been suggested. We tested the hypothesis that high FA (HFA) intake alters the adult mammary transcriptome in a manner consistent with increased potential for carcinogenesis, detectable beyond the period of intake. C57BL/6 mice were fed control FA (CFA) (1 mg/kg diet) or HFA (5 mg/kg diet) diets for 4 weeks, followed by AIN93M maintenance diet for 4 weeks. Plasma 5-methyltetrahydrofolate, p-aminobenzoylglutamate and unmetabolised FA concentrations were greater (1.62, 1.56, 5.80-fold, respectively) in HFA compared to CFA mice. RNA sequencing of the mammary transcriptome (~20 million reads) showed 222 transcripts (191 upregulated) differentially expressed between groups. Gene Set Enrichment showed upregulated genes significantly enriched in Epithelial Mesenchymal Transition, Myogenesis and Apical Junction and downregulated genes in E2F targets, MYC targets and G2M checkpoint. Cancer was the most altered Disease and Disorder pathway, with Metastasis, Mammary Tumour and Growth of Tumour the most upregulated pathways. ChIP-seq enrichment analysis showed that targets of histone methyltransferase EZH2 were enriched in HFA mice. This study demonstrates HFA intake during adulthood induces mammary transcriptome changes, consistent with greater tumorigenic potential.

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Distinct functions of dynamin isoforms in tumorigenesis and their potential as therapeutic targets in cancer

Cited by 23 publications

References 112 publications

Caveolin‑1 and dynamin‑2 overexpression is associated with the progression of bladder cancer

Caveolin‑1 and dynamin‑2 overexpression is associated with the progression of bladder cancer

Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients

Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice

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