Up-regulation of flotillin-2 is associated with renal cell carcinoma progression

Yang, Yan; Yang, Fenglian; Zhang, Haimin; Che, Jinxing; Zheng, Junhua

doi:10.1007/s13277-014-2343-9

Cited by 23 publications

(23 citation statements)

References 15 publications

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“…43 Flotillins have recently been implicated in the tumorigenesis of several cancers such as breast cancer, gastric cancer and renal cell carcinoma. [44][45][46] This study revealed an important function of flotillin-1 in H-Ras activation and invasion in breast cancer cells. In addition, our results from a xenograft model and clinical studies show that flotillin-1 may play a significant role in the tumorigenicity and aggressiveness of TNBC.…”

Section: Discussionmentioning

confidence: 72%

“…Mounting evidence suggests that flotillins may not be merely passive raft scaffolders, but active signaling molecules involved in several cellular processes . Flotillins have recently been implicated in the tumorigenesis of several cancers such as breast cancer, gastric cancer and renal cell carcinoma . This study revealed an important function of flotillin‐1 in H‐Ras activation and invasion in breast cancer cells.…”

Section: Discussionmentioning

confidence: 74%

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A novel role for flotillin‐1 in H‐Ras‐regulated breast cancer aggressiveness

Koh

Hao

Kim

et al. 2015

Intl Journal of Cancer

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Elevated expression and aberrant activation of Ras have been implicated in breast cancer aggressiveness. H-Ras, but not N-Ras, induces breast cell invasion. A crucial link between lipid rafts and H-Ras function has been suggested. This study sought to identify the lipid raft protein(s) responsible for H-Ras-induced tumorigenicity and invasiveness of breast cancer. We conducted a comparative proteomic analysis of lipid raft proteins from invasive MCF10A human breast epithelial cells engineered to express active H-Ras and non-invasive cells expressing active N-Ras. Here, we identified a lipid raft protein flotillin-1 as an important regulator of H-Ras activation and breast cell invasion. Flotillin-1 was required for epidermal growth factor-induced activation of H-Ras, but not that of N-Ras, in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Flotillin-1 knockdown inhibited the invasiveness of MDA-MB-231 and Hs578T TNBC cells in vitro and in vivo. In xenograft mouse tumor models of these TNBC cell lines, we showed that flotillin-1 played a critical role in tumor growth. Using human breast cancer samples, we provided clinical evidence for the metastatic potential of flotillin-1. Membrane staining of flotillin-1 was positively correlated with metastatic spread (p 5 0.013) and inversely correlated with patient disease-free survival rates (p 5 0.005). Expression of flotillin-1 was associated with H-Ras in breast cancer, especially in TNBC (p < 0.001). Our findings provide insight into the molecular basis of Ras isoform-specific interplay with flotillin-1, leading to tumorigenicity and aggressiveness of breast cancer.Breast cancer is one of the most frequent causes of death in women.1 Among breast cancers, triple-negative breast cancers (TNBCs) lacking estrogen receptor (ER), progesterone receptor (PR) and HER2 are associated with poor prognosis and tumor aggressiveness. 2 There are no effective drugs for this type of cancer at present.3 Cancer metastasis is an important cause of death in breast cancer patients. 4 Tumor invasion and metastasis are often associated with enhanced synthesis of matrix metalloproteinases (MMPs). [5][6][7]

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 74%

A novel role for flotillin‐1 in H‐Ras‐regulated breast cancer aggressiveness

Koh

Hao

Kim

et al. 2015

Intl Journal of Cancer

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“…FLOT2 was reported to be deregulated and associated with progression and poor survival in numerous types of cancer [24,25], making it a critical regulator of tumour initiation and prognosis. For example, the upregulation of FLOT2 was observed in renal cell carcinoma, and was association with poorer prognosis and overall survival of patients [26]. High expression of FLOT2 was also reported in cervical carcinoma and is associated with poor clinical survival of patients with cervical carcinoma [27].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma

Huang

Zheng

Huang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Flotillin-2 (FLOT2) was reported as oncogene and involves in the pathogenic process of several cancers, yet the precise mechanism of FLOT2 in glioma is still limited. In this study, we demonstrated that FLOT2 expression levels were greatly upregulated in glioma tissues and cell lines, and the FLOT2 expression in glioma tissue was markedly associated with tumour stage and size. Overexpression of FLOT2 was correlated with poor prognosis of glioma patients. The functional assay revealed that silenced FLOT2 repressed the viability, migration, and invasion of glioma cells. And then, we detected the relationship between miR-449 and FLOT2. Luciferase reporter assay and Western blot results showed that miR-449 directly binding the 3 0 UTR sequence of FLOT2 and regulated FLOT2 expression in glioma cells. Finally, we detected the expression levels of miR-449 in glioma tissue and cell lines and found that miR-449 was significantly downregulated in glioma tissues and cell lines. In conclusion, we demonstrated that overexpression FLOT2 was associated with poor prognosis of glioma patients and involved in the progression of glioma, identifying a novel prognostic biomarker and therapeutic target for glioma progression. ARTICLE HISTORY

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“…Flot2, a highly conserved 47-kDa protein located in a region on human chromosome 17q11.2, is originally characterized as an obbligato part of lipid raft domains that tether growth factor receptors linked to signal transduction pathways [30,31]. Recently, emerging evidence has demonstrated that Flot2 , a downstream gene of p53 family members [32], might be involved in the progression of metastasis in several kinds of solid tumors, including gastric carcinoma [33], breast cancer [34], renal cell carcinoma [35] and lung adenocarcinoma [36]. Zhao et al [37] recently suggested that in nasopharyngeal carcinoma, Flot2 is an indispensable member for transforming growth factor-β (TGF-β) family signaling, which epithelial cells receive from their micro-environment to drive EMT during cancer progression [38–40].…”

Section: Discussionmentioning

confidence: 99%

microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer

Wang

Shao

2017

Bioscience Reports

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miRNAs are a class of non-coding RNAs that exert critical roles in various biological processes. The aim of the present study was to identify the functional roles of miR-802 in regulating epithelial–mesenchymal transition (EMT) in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines (PC3 and DU145 cells) by qRT-PCR. Cell proliferation was detected using MTT assay, and cell apoptosis was evaluated using flow cytometry. Transwell assay was conducted to investigate cell migration and invasion. Expression analysis of a set of EMT markers was performed to explore whether miR-802 is involved in EMT program. Xenograft model was established to investigate the function of miR-802 in carcinogenesis in vivo. The direct regulation of Flotillin-2 (Flot2) by miR-802 was identified using luciferase reporter assay. miR-802 was remarkably down-regulated in PCa tissues and cell lines. Gain-of-function trails showed that miR-802 serves as an ‘oncosuppressor’ in PCa through inhibiting cell proliferation and promoting cell apoptosis in vitro. Overexpression of miR-802 significantly suppressed in vivo PCa tumor growth. Luciferase reporter analysis identified Flot2 as a direct target of miR-802 in PCa cells. Overexpressed miR-802 significantly suppressed EMT, migration and invasion in PCa cells by regulating Flot2. We identified miR-802 as a novel tumor suppressor in PCa progression and elucidated a novel mechanism of the miR-802/Flot2 axis in the regulation of EMT, which may be a potential therapeutic target.

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Up-regulation of flotillin-2 is associated with renal cell carcinoma progression

Cited by 23 publications

References 15 publications

A novel role for flotillin‐1 in H‐Ras‐regulated breast cancer aggressiveness

A novel role for flotillin‐1 in H‐Ras‐regulated breast cancer aggressiveness

RETRACTED ARTICLE: Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma

microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer

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