Extracellular gamma-synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion

Liu, Caiyun; Qu, Like; Zhao, Chuanke; Shou, Chengchao

doi:10.1186/s13046-018-0783-6

Cited by 17 publications

(10 citation statements)

References 51 publications

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“…(iii) γ-syn is abnormally expressed in various malignancies, but normal tissue, including breast, cervical, colon, prostate and ovarian cancers 52,53 . γ-syn promotes cancer cell migration and invasion 54 , and down regulating γ-syn expression by siRNA decreases cervical cancer proliferation in nude mice 55 . The role of synucleins in cancer is wide-open area of research.…”

Section: Discussionmentioning

confidence: 99%

Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth

Shekoohi

Rajasekaran

Patel

et al. 2021

Sci Rep

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The protein alpha-synuclein (α-syn) is unusual because, depending on its conformation and the type of cell in which it is expressed, it is pro-death or pro-survival, triggering neurodegeneration in Parkinson’s disease and enhancing cell survival of some melanomas. To probe the function of α-syn in melanoma, we used CRISPR/Cas9 to knockout SNCA, the gene that codes for α-syn, in SK-Mel-28 melanoma cells. The SNCA-knockout clones in culture exhibited a decrease in the transferrin receptor 1 (TfR1), an increase in ferritin, an increase of reactive oxygen species and proliferated slower than control cells. These SNCA-knockout clones grafted into SCID mice grew significantly slower than the SK-Mel-28 control cells that expressed α-syn. In the excised SNCA-knockout xenografts, TfR1 decreased 3.3-fold, ferritin increased 6.2-fold, the divalent metal ion transporter 1 (DMT1) increased threefold, and the iron exporter ferroportin (FPN1) decreased twofold relative to control xenografts. The excised SNCA-KO tumors exhibited significantly more ferric iron and TUNEL staining relative to the control melanoma xenografts. Collectively, depletion of α-syn in SK-Mel-28 cells dysregulates cellular iron metabolism, especially in xenografts, yielding melanoma cells that are deficient in TfR1 and FPN1, that accumulate ferric iron and ferritin, and that undergo apoptosis relative to control cells expressing α-syn.

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Section: Discussionmentioning

confidence: 99%

Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth

Shekoohi

Rajasekaran

Patel

et al. 2021

Sci Rep

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“…The multifaceted interactions of FAK with various signal transduction mediators may contribute to the FAK-dependent processes involved in cancer development [19]. Indeed, FAK action has been associated to aggressive cancer features as the cell adhesion and spreading [20–22], the enhancement of cell proliferation and survival [23, 24] and the facilitation of invasive cell phenotypes [25–27]. In this context, it is worth mentioning that FAK was shown to be over-expressed in a wide variety of human malignancies, including invasive and metastatic breast tumors [28–30].…”

Section: Introductionmentioning

confidence: 99%

Focal adhesion kinase (FAK) activation by estrogens involves GPER in triple-negative breast cancer cells

Rigiracciolo

Santolla

Lappano

et al. 2019

J Exp Clin Cancer Res

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BackgroundFocal adhesion kinase (FAK) is a cytoplasmatic protein tyrosine kinase that associates with both integrins and growth factor receptors toward the adhesion, migration and invasion of cancer cells. The G-protein coupled estrogen receptor (GPER) has been involved in the stimulatory action of estrogens in breast tumor. In this study, we have investigated the engagement of FAK by GPER signaling in triple negative breast cancer (TNBC) cells.MethodsPublicly available large-scale database and patient data sets derived from “The Cancer Genome Atlas” (TCGA; www.cbioportal.org) were used to assess FAK expression in TNBC, non-TNBC tumors and normal breast tissues. MDA-MB 231 and SUM159 TNBC cells were used as model system. The levels of phosphorylated FAK, other transduction mediators and target genes were detected by western blotting analysis. Focal adhesion assay was carried out in order to determine the focal adhesion points and the formation of focal adhesions (FAs). Luciferase assays were performed to evaluate the promoters activity of c-FOS, EGR1 and CTGF upon GPER activation. The mRNA expression of the aforementioned genes was measured by real time-PCR. Boyden chamber and wound healing assays were used in order to evaluate cell migration. The statistical analysis was performed by ANOVA.ResultsWe first determined by bioinformatic analysis that the mRNA expression levels of the gene encoding FAK, namely PTK2, is higher in TNBC respect to non-TNBC and normal breast tissues. Next, we found that estrogenic GPER signaling triggers Y397 FAK phosphorylation as well as the increase of focal adhesion points (FAs) in TNBC cells. Besides, we ascertained that GPER and FAK activation are involved in the STAT3 nuclear accumulation and gene expression changes. As biological counterpart, we show that FAK inhibition prevents the migration of TNBC cells upon GPER activation.ConclusionsThe present data provide novel insights regarding the action of FAK in TNBC. Moreover, on the basis of our findings estrogenic GPER signaling may be considered among the transduction mechanisms engaging FAK toward breast cancer progression.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1056-8) contains supplementary material, which is available to authorized users.

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“…Evidence suggests that long noncoding RNAs (lncRNAs) play an important role in the regulation of several biological processes related to hepatocarcinogenesis, including cell proliferation, apoptosis, metastasis, angiogenesis, and chemosensitivity (Lin et al, 2018;Deng et al, 2015;Zhuang et al, 2019;. Many lncRNAs play crucial roles in the oncogenesis and development of malignant tumours and function as oncogenes or tumour suppressors (Bach & Lee, 2018).…”

Section: Introductionmentioning

confidence: 99%

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

Wei

Huang

Zhang

et al. 2020

PeerJ

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Background Aberrant expression of long noncoding RNAs are implicated in the pathogenesis of human malignancies. LINC00844 expression is dramatically downregulated in prostate cancer, and functional studies have revealed the association between the aberrant expression of LINC00844 and prostate cancer cell invasion and metastasis. However, the function and mechanism of action of LINC00844 in the pathogenesis of hepatocellular carcinoma (HCC) are poorly understood. Methods LINC00844 and N-Myc downstream-regulated 1 (NDRG1) expression in HCC tissues and cell lines was detected with real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Correlations between LINC00844 expression level and clinicopathological features were investigated using the original data from The Cancer Genome Atlas (TCGA) database. HepG2 and HCCLM9 cell lines were transfected with Lv-LIN00844 virus to obtain LINC00844-overexpressing cell lines. Cell proliferation and cell invasion and migration were examined with the cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, the correlation between LINC00844 and NDRG1 expression was analysed using Pearson’s correlation analysis. Results LINC00844 expression was significantly downregulatedin HCC tissues and cell lines, and a statistical correlation was detected between low LINC00844 expression and sex (Female), advanced American Joint Committee on Cancer (AJCC) stage (III + IV), histological grade (G3 + G4), and vascular invasion (Micro and Macro). In vitro experiments showed that LINC00844 overexpression significantly repressed the proliferation, migration, and invasion of HCC cells. NDRG1 expression was higher in HCC tissues and LINC00844 could partly inhibit the expression of NDRG1.

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Extracellular gamma-synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion

Cited by 17 publications

References 51 publications

Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth

Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth

Focal adhesion kinase (FAK) activation by estrogens involves GPER in triple-negative breast cancer cells

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

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