Full Text:   <2805>

Summary:  <2296>

CLC number: R739.6

On-line Access: 2018-03-05

Received: 2017-02-23

Revision Accepted: 2017-07-12

Crosschecked: 2018-02-07

Cited: 0

Clicked: 6932

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xu-xu Liu

https://orcid.org/0000-0002-2387-0653

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.3 P.171-182

http://doi.org/10.1631/jzus.B1700102


Roles of flotillins in tumors


Author(s):  Xu-xu Liu, Wei-dong Liu, Lei Wang, Bin Zhu, Xiao Shi, Zi-xuan Peng, He-cheng Zhu, Xing-dong Liu, Mei-zuo Zhong, Dan Xie, Mu-sheng Zeng, Cai-ping Ren

Affiliation(s):  Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Central South University, Changsha 410078, China; more

Corresponding email(s):   rencaiping@csu.edu.cn

Key Words:  Flotillins, Tumor, Lipid raft protein, Signal transduction


Share this article to: More |Next Article >>>

Xu-xu Liu, Wei-dong Liu, Lei Wang, Bin Zhu, Xiao Shi, Zi-xuan Peng, He-cheng Zhu, Xing-dong Liu, Mei-zuo Zhong, Dan Xie, Mu-sheng Zeng, Cai-ping Ren. Roles of flotillins in tumors[J]. Journal of Zhejiang University Science B, 2018, 19(3): 171-182.

@article{title="Roles of flotillins in tumors",
author="Xu-xu Liu, Wei-dong Liu, Lei Wang, Bin Zhu, Xiao Shi, Zi-xuan Peng, He-cheng Zhu, Xing-dong Liu, Mei-zuo Zhong, Dan Xie, Mu-sheng Zeng, Cai-ping Ren",
journal="Journal of Zhejiang University Science B",
volume="19",
number="3",
pages="171-182",
year="2018",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1700102"
}

%0 Journal Article
%T Roles of flotillins in tumors
%A Xu-xu Liu
%A Wei-dong Liu
%A Lei Wang
%A Bin Zhu
%A Xiao Shi
%A Zi-xuan Peng
%A He-cheng Zhu
%A Xing-dong Liu
%A Mei-zuo Zhong
%A Dan Xie
%A Mu-sheng Zeng
%A Cai-ping Ren
%J Journal of Zhejiang University SCIENCE B
%V 19
%N 3
%P 171-182
%@ 1673-1581
%D 2018
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700102

TY - JOUR
T1 - Roles of flotillins in tumors
A1 - Xu-xu Liu
A1 - Wei-dong Liu
A1 - Lei Wang
A1 - Bin Zhu
A1 - Xiao Shi
A1 - Zi-xuan Peng
A1 - He-cheng Zhu
A1 - Xing-dong Liu
A1 - Mei-zuo Zhong
A1 - Dan Xie
A1 - Mu-sheng Zeng
A1 - Cai-ping Ren
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 3
SP - 171
EP - 182
%@ 1673-1581
Y1 - 2018
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1700102


Abstract: 
The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer patients. The lipid raft marker proteins, flotillin-1 and flotillin-2, were first found in goldfish retinal ganglion cells during axon regeneration. They have since been found in a variety of cells, mainly on the inner surface of cell membranes, and not only act as a skeleton to provide a platform for protein–protein interactions, but also are involved in signal transduction, nerve regeneration, endocytosis, and lymphocyte activation. Previous studies have shown that flotillins are closely associated with tumor development, invasion, and metastasis. In this article, we review the functions of flotillins in relevant cell processes, their underlying mechanisms of action in a variety of tumors, and their potential applications to tumor molecular diagnosis and targeted therapy.

脂筏标记蛋白flotillins在肿瘤中的研究进展

概要:本文旨在对flotillins在相关细胞进程中的作用、在多种肿瘤中的作用和机制及其在肿瘤分子诊断和靶向治疗等方面的潜在应用价值进行综述.图1以示意图的形式直观地展示flotillin-1和flotillin-2的蛋白结构;表1对flotillin-1和flotillin-2在各种肿瘤中的表达异常情况、发挥的生物学功能及其机制进行汇总;在图2中,以模式图的形式展示flotillin-1和flotillin-2在肿瘤细胞中参与的信号通路及导致肿瘤细胞出现的不同表型.许多研究表明,flotillins在多种肿瘤中过表达,并且与肿瘤的发生发展、分期和转移密切相关.转移标志着肿瘤由局部病变发展为不可治愈的系统病变,是肿瘤预后的一个重要影响因素,但是其机制尚未完全阐述.因此,对其机制进行进一步探索有助于促进恶性肿瘤分子诊断、预后和精准治疗的发展.
关键词:Flotillins;肿瘤;脂筏标记蛋白;信号传导

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Affentranger S, Martinelli S, Hahn J, et al., 2011. Dynamic reorganization of flotillins in chemokine-stimulated human T-lymphocytes. BMC Cell Biol, 12:28.

[2]Ait-Slimane T, Galmes R, Trugnan G, et al., 2009. Basolateral internalization of GPI-anchored proteins occurs via a clathrin-independent flotillin-dependent pathway in polarized hepatic cells. Mol Biol Cell, 20(17):3792-3800.

[3]Amaddii M, Meister M, Banning A, et al., 2012. Flotillin-1/reggie-2 protein plays dual role in activation of receptor-tyrosine kinase/mitogen-activated protein kinase signaling. J Biol Chem, 287(10):7265-7278.

[4]Asp N, Pust S, Sandvig K, 2014. Flotillin depletion affects ErbB protein levels in different human breast cancer cells. Biochim Biophys Acta, 1843(9):1987-1996.

[5]Babuke T, Ruonala M, Meister M, et al., 2009. Hetero-oligomerization of reggie-1/flotillin-2 and reggie-2/flotillin-1 is required for their endocytosis. Cell Signal, 21(8):1287-1297.

[6]Banning A, Regenbrecht CRA, Tikkanen R, 2014. Increased activity of mitogen activated protein kinase pathway in flotillin-2 knockout mouse model. Cell Signal, 26(2):198-207.

[7]Baumann CA, Ribon V, Kanzaki M, et al., 2000. CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature, 407(6801):202-207.

[8]Berger T, Ueda T, Arpaia E, et al., 2013. Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model. Oncogene, 32(41):4989-4994.

[9]Bickel PE, Scherer PE, Schnitzer JE, et al., 1997. Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. J Biol Chem, 272(21):13793-13802.

[10]Bitsikas V, Riento K, Howe JD, et al., 2014. The role of flotillins in regulating Aβ production, investigated using flotillin 1−/−, flotillin 2−/− double knockout mice. PLoS ONE, 9(1):e85217.

[11]Cao K, Xie D, Cao P, et al., 2014. SiRNA-mediated flotillin-2 (Flot2) downregulation inhibits cell proliferation, migration, and invasion in gastric carcinoma cells. Oncol Res, 21(5):271-279.

[12]Cho YJ, Chema D, Moskow JJ, et al., 1995. Epidermal surface antigen (MS17S1) is highly conserved between mouse and human. Genomics, 27(2):251-258.

[13]Cremona ML, Matthies HJ, Pau K, et al., 2011. Flotillin-1 is essential for PKC-triggered endocytosis and membrane microdomain localization of DAT. Nat Neurosci, 14(4):469-477.

[14]de Gassart A, Géminard C, Février B, et al., 2003. Lipid raft-associated protein sorting in exosomes. Blood, 102(13):4336-4344.

[15]Dermine JF, Duclos S, Garin J, et al., 2001. Flotillin-1- enriched lipid raft domains accumulate on maturing phagosomes. J Biol Chem, 276(21):18507-18512.

[16]Doherty SD, Prieto VG, George S, et al., 2006. High flotillin-2 expression is associated with lymph node metastasis and Breslow depth in melanoma. Melanoma Res, 16(5):461-463.

[17]Edgar AJ, Polak JM, 2001. Flotillin-1: gene structure: cDNA cloning from human lung and the identification of alternative polyadenylation signals. Int J Biochem Cell Biol, 33(1):53-64.

[18]Fecchi K, Volonte D, Hezel MP, et al., 2006. Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3 in skeletal muscle cells. FASEB J, 20(6):705-707.

[19]Galbiati F, Volonté D, Goltz JS, et al., 1998. Identification, sequence and developmental expression of invertebrate flotillins from Drosophila melanogaster. Gene, 210(2):229-237.

[20]Gao W, Xu J, Wang F, et al., 2015. Plasma membrane proteomic analysis of human gastric cancer tissues: revealing flotillin 1 as a marker for gastric cancer. BMC Cancer, 15(1):367.

[21]Gómez V, Sesé M, Santamaría A, et al., 2010. Regulation of Aurora B kinase by the lipid raft protein flotillin-1. J Biol Chem, 285(27):20683-20690.

[22]Hazarika P, McCarty MF, Prieto VG, et al., 2004. Up-regulation of flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res, 64(20):7361-7369.

[23]Jemal A, Bray F, Center MM, et al., 2011. Global cancer statistics. CA Cancer J Clin, 61(2):69-90.

[24]Kang M, Ren MP, Zhao L, et al., 2015. miR-485-5p acts as a negative regulator in gastric cancer progression by targeting flotillin-1. Am J Transl Res, 7(11):2212-2222.

[25]Koch JC, Solis GP, Bodrikov V, et al., 2013. Upregulation of reggie-1/flotillin-2 promotes axon regeneration in the rat optic nerve in vivo and neurite growth in vitro. Neurobiol Dis, 51:168-176.

[26]Kurrle N, Ockenga W, Meister M, et al., 2013. Phosphatidylinositol 3-kinase dependent upregulation of the epidermal growth factor receptor upon flotillin-1 depletion in breast cancer cells. BMC Cancer, 13:575.

[27]Langhorst MF, Reuter A, Luxenhofer G, et al., 2006. Preformed reggie/flotillin caps: stable priming platforms for macrodomain assembly in T cells. FASEB J, 20(6):711-713.

[28]Leemans CR, Braakhuis BJ, Brakenhoff RH, 2011. The molecular biology of head and neck cancer. Nat Rev Cancer, 11(1):9-22.

[29]Li H, Zhang Y, Chen SW, et al., 2014. Prognostic significance of flotillin1 expression in clinically N0 tongue squamous cell cancer. Int J Clin Exp Pathol, 7(3):996-1003.

[30]Li L, Luo J, Wang B, et al., 2013. MicroRNA-124 targets flotillin-1 to regulate proliferation and migration in breast cancer. Mol Cancer, 12:163.

[31]Li Z, Yang Y, Gao Y, et al., 2015. Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer. Am J Cancer Res, 6(1):38-50.

[32]Lin C, Wu Z, Lin X, et al., 2011. Knockdown of FLOT1 impairs cell proliferation and tumorigenicity in breast cancer through upregulation of FOXO3a. Clin Cancer Res, 17(10):3089-3099.

[33]Liu J, DeYoung SM, Zhang M, et al., 2005. The stomatin/prohibitin/flotillin/HflK/C domain of flotillin-1 contains distinct sequences that direct plasma membrane localization and protein interactions in 3T3-L1 adipocytes. J Biol Chem, 280(16):16125-16134.

[34]Liu J, Huang W, Ren C, et al., 2015. Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways. Sci Rep, 5: 11614.

[35]Liu R, Xie H, Luo C, et al., 2015. Identification of FLOT2 as a novel target for microRNA-34a in melanoma. J Cancer Res Clin Oncol, 141(6):993-1006.

[36]Liu Y, Lin L, Huang Z, et al., 2015. High expression of flotillin-2 is associated with poor clinical survival in cervical carcinoma. Int J Clin Exp Pathol, 8(1):622-628.

[37]Ludwig A, Otto GP, Riento K, et al., 2010. Flotillin microdomains interact with the cortical cytoskeleton to control uropod formation and neutrophil recruitment. J Cell Biol, 191(4):771-781.

[38]Mao L, Hong WK, Papadimitrakopoulou VA, 2004. Focus on head and neck cancer. Cancer Cell, 5(4):311-316.

[39]Mitra P, Zheng X, Czech MP, 2004. RNAi-based analysis of CAP, Cbl, and CrkII function in the regulation of GLUT4 by insulin. J Biol Chem, 279(36):37431-37435.

[40]Morrow IC, Parton RG, 2005. Flotillins and the PHB domain protein family: rafts, worms and anaesthetics. Traffic, 6(9):725-740.

[41]Munderloh C, Solis GP, Bodrikov V, et al., 2009. Reggies/flotillins regulate retinal axon regeneration in the zebrafish optic nerve and differentiation of hippocampal and N2a neurons. J Neurosci, 29(20):6607-6615.

[42]Perou CM, Sørlie T, Eisen MB, et al., 2000. Molecular portraits of human breast tumours. Nature, 406(6797):747-752.

[43]Punyadeera C, Dassen H, Klomp J, et al., 2005. Oestrogen-modulated gene expression in the human endometrium. Cell Mol Life Sci, 62(2):239-250.

[44]Pust S, Klokk TI, Musa N, et al., 2013. Flotillins as regulators of ErbB2 levels in breast cancer. Oncogene, 32(29):3443-3451.

[45]Rivera-Milla E, Stuermer CA, Málaga-Trillo E, 2006. Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain. Cell Mol Life Sci, 63(3):343-357.

[46]Santamaria A, Castellanos E, Gómez V, et al., 2005. PTOV1 enables the nuclear translocation and mitogenic activity of flotillin-1, a major protein of lipid rafts. Mol Cell Biol, 25(5):1900-1911.

[47]Saslowsky DE, Cho JA, Chinnapen H, et al., 2010. Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2. J Clin Invest, 120(12):4399-4409.

[48]Satyamoorthy K, Li G, Gerrero MR, et al., 2003. Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res, 63(4):756-759.

[49]Schroeder WT, Stewart-Galetka S, Mandavilli S, et al., 1994. Cloning and characterization of a novel epidermal cell surface antigen (ESA). J Biol Chem, 269(31):19983-19991.

[50]Schulte T, Paschke KA, Laessing U, et al., 1997. Reggie-1 and reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration. Development, 124(2):577-587.

[51]Siegel R, Naishadham D, Jemal A, 2013. Cancer statistics, 2013. CA Cancer J Clin, 63(1):11-30.

[52]Song L, Gong H, Lin C, et al., 2012. Flotillin-1 promotes tumor necrosis factor-α receptor signaling and activation of NF-κB in esophageal squamous cell carcinoma cells. Gastroenterology, 143(4):995-1005.e12.

[53]Stuermer CA, 2010. The reggie/flotillin connection to growth. Trends Cell Biol, 20(1):6-13.

[54]Stuermer CA, 2012. How reggies regulate regeneration and axon growth. Cell Tissue Res, 349(1):71-77.

[55]Takano N, Iizuka N, Hazama S, et al., 2002. Expression of estrogen receptor-α and -β mRNAs in human gastric cancer. Cancer Lett, 176(2):129-135.

[56]Vincent-Chong VK, Salahshourifar I, Karen-Ng LP, et al., 2014. Overexpression of MMP13 is associated with clinical outcomes and poor prognosis in oral squamous cell carcinoma. Sci World J, 2014:897523.

[57]Wang X, Yang Q, Guo L, et al., 2013. Flotillin-2 is associated with breast cancer progression and poor survival outcomes. J Transl Med, 11(1):190.

[58]Wang YL, Yao WJ, Guo L, et al., 2015. Expression of flotillin-2 in human non-small cell lung cancer and its correlation with tumor progression and patient survival. Int J Clin Exp Pathol, 8(1):601-607.

[59]Wen Q, Li J, Wang W, et al., 2014. Increased expression of flotillin-2 protein as a novel biomarker for lymph node metastasis in nasopharyngeal carcinoma. PLoS ONE, 9(7):e101676.

[60]Xie G, Li J, Chen J, et al., 2015. Knockdown of flotillin-2 impairs the proliferation of breast cancer cells through modulation of Akt/FOXO signaling. Oncol Rep, 33(5):2285-2290.

[61]Xie S, Xu H, Shan X, et al., 2015. Clinicopathological and prognostic significance of survivin expression in patients with oral squamous cell carcinoma: evidence from a meta-analysis. PLoS ONE, 10(2):e0116517.

[62]Yan Y, Yang FQ, Zhang HM, et al., 2014. Up-regulation of flotillin-2 is associated with renal cell carcinoma progression. Tumor Biol, 35(10):10479-10486.

[63]Yang XY, Ren CP, Wang L, et al., 2005. Identification of differentially expressed genes in metastatic and non-metastatic nasopharyngeal carcinoma cells by suppression subtractive hybridization. Cell Oncol, 27(4):215-223.

[64]Zagouri F, Sergentanis TN, Chrysikos D, et al., 2012. Molecularly targeted therapies in cervical cancer. A systematic review. Gynecol Oncol, 126(2):291-303.

[65]Zhang SH, Wang CJ, Shi L, et al., 2013. High expression of FLOT1 is associated with progression and poor prognosis in hepatocellular carcinoma. PLoS ONE, 8(6):e64709.

[66]Zhang Y, Li H, Han J, et al., 2015. Down-regulation of microRNA-124 is correlated with tumor metastasis and poor prognosis in patients with lung cancer. Int J Clin Exp Pathol, 8(2):1967-1972.

[67]Zhao L, Lin L, Pan C, et al., 2015. Flotillin-2 promotes nasopharyngeal carcinoma metastasis and is necessary for the epithelial-mesenchymal transition induced by transforming growth factor-β. Oncotarget, 6(12):9781-9793.

[68]https://doi.org/10.18632/oncotarget.3382

[69]Zhu Z, Wang J, Sun Z, et al., 2013. Flotillin2 expression correlates with HER2 levels and poor prognosis in gastric cancer. PLoS ONE, 8(5):e62365.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE