Overexpression and translocation of dynamin 2 promotes tumor aggressiveness in breast carcinomas

Sajed, Roya; Zanjani, Leili Saeednejad; Rahimi, Mandana; Mansoori, Maryam; Zarnani, Amir‐Hassan; Madjd, Zahra; Ghods, Roya

doi:10.17179/excli2020-2762

Cited by 4 publications

(3 citation statements)

References 45 publications

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“…Xu et al, [18] also reported that dynamin 2 expression significantly increased during the stages of prostate cancer . It has been reported that dynamin 2 expression was association with more aggressive tumor behavior and more advanced disease in the patients with breast cancer [19]. Therefore, dynamin 2 molecule could be considered as an indicator of disease progression and aggressiveness.…”

Section: Results Patients' Characteristicsmentioning

confidence: 98%

Dynamin-2 and Angiopoietin-like protein 2 as novel prognostic markers in papillary thyroid carcinoma

Hafez

Abdelbary

Elsebai³

et al. 2021

Zagazig University Medical Journal

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Background: Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid cancer. Fortunately, most PTC patients have favorable outcomes, but about 20% of patients,have distant metastases. Therefore, the exploration of new biomarkers to know new characteristics of PTC should be updated. The aim of our study is to evaluate the possible role of Dynamin-2 and Angiopoietin-like protein 2 (Anglp2) as novel prognostic markers for papillary thyroid carcinoma. Material and Methods: In our study, we investigated the expression of DNM2 and Anglp2 in 60 cases of PTC . The clinical significance of the markers was evaluated by assessing correlation with the clinicopathological parameters. Results: High DNM2 expression PTC was significantly associated with advanced tumor stage, lymph node metastasis, recurrence and death ( p<0.002,0.018, <0.001, <0.001respectivelly).High expression levels of Anglp2 in PTC were significantly associated with advanced tumor stage, , recurrence and death (p <0.004, ,p= 0.004,p=0.003 respectively). Conclusions: DNM2 and Anglp2 were independent PTC markers indicating more likely recurrence and poor prognosis. Expression may help to select the high-risk patients for adjuvant targeted therapy.

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Section: Results Patients' Characteristicsmentioning

confidence: 98%

Dynamin-2 and Angiopoietin-like protein 2 as novel prognostic markers in papillary thyroid carcinoma

Hafez

Abdelbary

Elsebai³

et al. 2021

Zagazig University Medical Journal

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“…The internelization of the liganed-receptor complex involves several endocytosis-related proteins including Dyn2. In addition to its integral role in RME, some investigations demosnstrated that Dyn2 overexpression is associated with more aggressive tumor phenotype in breast cancer patients, indicating its role as an indicator of disease progression and aggressiveness [ 28 ]. Herein, Dyn2 was selectively inhibited by Dynasore (DYN), that interacts with the G domain of Dyn2 to prohibit its internsic GTPase activity.…”

Section: Discussionmentioning

confidence: 99%

Vasopressin induces apoptosis but does not enhance the antiproliferative effect of dynamin 2 or PI3K/Akt inhibition in luminal A breast cancer cells

et al. 2022

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Breast cancer cells abnormally express vasopressin (AVP) and its receptors. The effect of AVP is largely orchestrated through its downstream signaling and by receptor-mediated endocytosis (RME), in which Dynamin 2 (Dyn2) plays an integral role in vesicle closure. In this work, luminal A breast cancer cells were treated with AVP, and then Dynasore (DYN) was employed to inhibit Dyn2 to explore the combined effect of AVP and Dyn2 inhibition on the survival of breast cancer cells. The results revealed that DYN alone demonstrated a concentration-dependent cytotoxic effect in AVP untreated cells. Apoptosis developed in 29.7 and 30.3% of cells treated with AVP or AVP+DYN, respectively, compared to 32.5% in cells treated with Wortmannin (Wort, a selective PI3K pathway inhibitor). More apoptosis was observed when cells were treated with DYN+Wort in presence or absence of exogenous AVP. Besides, 2 or 4- fold increases in the expression of Bax and Caspase-3, were observed in cells exposed to AVP in absence or presence of DYN, respectively. This was associated with higher levels of the autophagy marker (LC3II protein). Meanwhile, the activation of Akt protein, sequentially decreased in the same pattern. Cell’s invasion decreased when they were exposed to AVP alone or combined with DYN or/and Wort. Conclusively, although many reports suggested the proliferative effect of AVP, the results predict the antiproliferative and antimetastatic effects of 100 nM AVP in luminal A breast cancer cells. However, the hormone did not enhance the cytotoxic effect of Dyn 2 or PI3K pathway inhibition. Graphical Abstract Summary of the Dynamin 2 independent AVP antiproliferative effects. Breast cancer cells expresses AVP as a Prohormone (A). At high dose of AVP, the hormone is liganded with AVP receptor (B) to initiate RME, where the endosomed complex (C) is degraded through the endosome-lysosome system, as a part of signal management. These events consume soluble Dyn2 in neck closure and vesicle fission (D). This makes the cells more substitutable to the direct apoptotic effect of DYN (E). Alternatively, at lower AVP doses the liganded AVP may initiate cAMP-mediated downstream signaling (F) and cellular proliferation. In parallel, Wort inhibits PIP2-PIP3 conversion (G) and the subsequent inhibition of PI3K/Akt/mTOR pathway leading to cell death.

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“…Apart from sCNA, translocations, fusions and extra chromosomal gene amplifications equally play substantial roles in defining the net clinical disease phenotypes (18–22). Furthermore, early onset of cancer, at least in some cancer entities such as colorectal and gastric cancers is associated with aggressive disease profiles (23, 24).…”

Section: Introductionmentioning

confidence: 99%

SOX2dosage sustains tumor-promoting inflammation to drive disease aggressiveness by modulating theFOSL2/IL6axis

Njouendou

Tiofack

Kenfack

et al. 2022

Preprint

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BackgroundInflammation is undoubtedly a hallmark of cancer development. Its maintenance within tumors and subsequent consequences on disease aggressiveness is less understood.MethodsMulti-omic analyses of 27 (~ 5000 samples) entities from the TCGA, GEO and in-house data was performed to investigate the molecular determinant of tumor aggressiveness. Using molecular loss of function data, the mechanistic underpinnings of inflammation-induced tumor aggressiveness was addressed.ResultsThe data revealed a significant association between somatic copy number alterations (sCNA) and tumor aggressiveness, with amplification of the transcription factorSOX2being the most important feature among novel and known aggressiveness-associated genes such asZIC5andMYEOV.Mechanistically,SOX2regulates a group of aggressiveness-related genes including theAP1transcription factorFOSL2to sustain pro-inflammatory pathway such asIL6-JAK-STAT3, TNFAandIL17signaling pathways. Prolonged inflammation induces immunosuppression and further leads to activation of cytidine deamination and consequential DNA damage evidenced by enrichment in cytidine deamination mutational signatures in aggressive tumors.The resulting DNA damage affects tumor suppressor genes such asTP53,which was the most mutated gene in aggressive tumors compared with less aggressive tumors (38% vs 14%), thereby releasing cell cycle control. This was exemplified in Glioblastoma multiform, whereTP53andIDH1mutations are predominant.IDH1mutations were almost only seen in younger patients (>45 years, > 90%) and may explain the previously reported favorable prognosis.ConclusionTaken together, our data demonstrate the implication ofSOX2in promoting DNA damage and genome instability by sustaining inflammation viaFOSL2/IL6,resulting in tumor aggressiveness.

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Overexpression and translocation of dynamin 2 promotes tumor aggressiveness in breast carcinomas

Cited by 4 publications

References 45 publications

Dynamin-2 and Angiopoietin-like protein 2 as novel prognostic markers in papillary thyroid carcinoma

Dynamin-2 and Angiopoietin-like protein 2 as novel prognostic markers in papillary thyroid carcinoma

Vasopressin induces apoptosis but does not enhance the antiproliferative effect of dynamin 2 or PI3K/Akt inhibition in luminal A breast cancer cells

SOX2dosage sustains tumor-promoting inflammation to drive disease aggressiveness by modulating theFOSL2/IL6axis

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