title: Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma.
abstract: Rhabdomyosarcoma (RMS) is a childhood soft tissue tumor with broad expression of markers that are typically found in skeletal muscle. Cavin-1 is a recently discovered protein actively cooperating with Caveolin-1 (Cav-1) in the morphogenesis of caveolae and whose role in cancer is drawing increasing attention. Using a combined in silico and in vitro analysis here we show that Cavin-1 is expressed in myogenic RMS tumors as well as in human and primary mouse RMS cultures, exhibiting a broad subcellular localization, ranging from nuclei and cytosol to plasma membrane. In particular, the coexpression and plasma membrane interaction between Cavin-1 and Cav-1 characterized the proliferation of human and mouse RMS cell cultures, while a downregulation of their expression levels was observed during the myogenic differentiation. Knockdown of Cavin-1 or Cav-1 in the human RD and RH30 cells led to impairment of cell proliferation and migration. Moreover, loss of Cavin-1 in RD cells impaired the anchorage-independent cell growth in soft agar. While the loss of Cavin-1 did not affect the Cav-1 protein levels in RMS cells, Cav-1 overexpression and knockdown triggered a rise or depletion of Cavin-1 protein levels in RD cells, respectively, in turn reflecting on increased or decreased cell proliferation, migration and anchorage-independent cell growth. Collectively, these data indicate that the interaction between Cavin-1 and Cav-1 underlies the cell growth and migration in myogenic tumors.
authors.affiliation: 1] Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy [2] Interuniversity Institute of Myology (IIM), Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Faggi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Chiarelli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mitola
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ronca
authors.affiliation: 1] Interuniversity Institute of Myology (IIM), Rome, Italy [2] Unit of Histology and IIM, Sapienza University, DAHFMO, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Madaro
authors.affiliation: 1] Interuniversity Institute of Myology (IIM), Rome, Italy [2] Unit of Histology and IIM, Sapienza University, DAHFMO, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bouche
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Poliani
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Vezzoli
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Longhena
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Monti
authors.affiliation: Department of Endocrinology and Medicine, University of Genoa, Genoa, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Salani
authors.affiliation: Department of Endocrinology and Medicine, University of Genoa, Genoa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Maggi
authors.affiliation: 1] Department of Pediatrics, Oregon Health Science University, Portland, OR, USA [2] Children's Cancer Therapy Development Institute, Portland, OR, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Keller
authors.affiliation: 1] Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy [2] Interuniversity Institute of Myology (IIM), Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fanzani
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism
chemical_list: C497835:CAVIN1 protein, human; D051242:Caveolin 1; C112745:Cavin1 protein, mouse; D008565:Membrane Proteins; D016601:RNA-Binding Proteins
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20002-7
references.pmid: 22135462
references.citation: Biochem J. 2000 Apr 1;347 Pt 1:55-9
references.pmid: 10727401
references.citation: Invasion Metastasis. 1991;11(2):116-24
references.pmid: 1917385
references.citation: J Clin Invest. 2009 Nov;119(11):3395-407
references.pmid: 19809159
references.citation: Am J Pathol. 2010 Jan;176(1):416-34
references.pmid: 20019182
references.citation: J Biol Chem. 2008 Feb 15;283(7):4314-22
references.pmid: 18056712
references.citation: Cancer Res. 1989 Nov 15;49(22):6324-7
references.pmid: 2680062
references.citation: Mol Cancer. 2006 Aug 09;5:31
references.pmid: 16899113
references.citation: Am J Med Genet A. 2010 Sep;152A(9):2245-53
references.pmid: 20684003
references.citation: Gene. 2001 Aug 22;274(1-2):139-49
references.pmid: 11675006
references.citation: PLoS One. 2012;7(8):e43041
references.pmid: 22912783
references.citation: Nat Rev Mol Cell Biol. 2007 Mar;8(3):185-94
references.pmid: 17318224
references.citation: Nucleic Acids Res. 2001 Jan 15;29(2):423-9
references.pmid: 11139612
references.citation: Clin Genet. 2010 May;77(5):436-7
references.pmid: 20447152
references.citation: Nat Protoc. 2008;3(7):1125-31
references.pmid: 18600217
references.citation: J Cell Mol Med. 2011 Dec;15(12):2553-68
references.pmid: 21707915
references.citation: Biochimie. 2011 Jan;93(1):71-7
references.pmid: 20363285
references.citation: Eur J Cell Biol. 2011 Feb-Mar;90(2-3):136-42
references.pmid: 20732728
references.citation: Genes Dev. 2004 Nov 1;18(21):2608-13
references.pmid: 15520281
references.citation: Cancer Res. 1992 Apr 15;52(8):2243-7
references.pmid: 1559227
references.citation: Trends Mol Med. 2013 Sep;19(9):546-54
references.pmid: 23890422
references.citation: Cell Tissue Res. 2001 Jul;305(1):99-106
references.pmid: 11512676
references.citation: Mol Cancer Ther. 2009 Mar;8(3):543-51
references.pmid: 19258428
references.citation: Oncotarget. 2013 Oct;4(10):1844-55
references.pmid: 24123650
references.citation: J Clin Invest. 2009 Sep;119(9):2623-33
references.pmid: 19726876
references.citation: Mol Genet Metab. 2010 Oct-Nov;101(2-3):233-7
references.pmid: 20638880
references.citation: Nat Genet. 2014 Jun;46(6):601-6
references.pmid: 24793134
references.citation: Cancer Res. 2005 Jun 1;65(11):4490-5
references.pmid: 15930263
references.citation: Biochem Biophys Res Commun. 2006 Nov 24;350(3):657-61
references.pmid: 17026959
references.citation: Mol Cell Proteomics. 2012 Feb;11(2):M111.012245
references.pmid: 22030351
references.citation: Cancer Discov. 2014 Feb;4(2):216-31
references.pmid: 24436047
references.citation: Eur J Cancer. 2011 Mar;47(5):761-72
references.pmid: 21106364
references.citation: Cancer Metastasis Rev. 2008 Dec;27(4):715-35
references.pmid: 18506396
references.citation: Genes Dev. 2007 Jun 1;21(11):1382-95
references.pmid: 17510286
references.citation: J Biol Chem. 2011 Aug 19;286(33):28657-61
references.pmid: 21705337
references.citation: Nat Genet. 1993 Nov;5(3):230-5
references.pmid: 8275086
references.citation: Oncogene. 2014 Jul 3;33(27):3561-70
references.pmid: 23934189
references.citation: Cell Res. 2011 Jul;21(7):1088-101
references.pmid: 21445100
references.citation: J Biol Chem. 2014 Mar 21;289(12):8473-83
references.pmid: 24509860
references.citation: PLoS One. 2012;7(3):e33752
references.pmid: 22461895
references.citation: Diabetes. 2011 Mar;60(3):757-65
references.pmid: 21282370
references.citation: PLoS Genet. 2010 Mar 12;6(3):e1000874
references.pmid: 20300641
references.citation: Cytogenet Cell Genet. 1987;45(3-4):148-55
references.pmid: 3691179
references.citation: Cancer Cell. 2011 Feb 15;19(2):177-91
references.pmid: 21316601
references.citation: Cancer Res. 2005 Sep 1;65(17 ):7530-2
references.pmid: 16140913
references.citation: Pol J Pathol. 2011 Dec;62(4):262-8
references.pmid: 22246913
references.citation: Semin Radiat Oncol. 2010 Jan;20(1):45-51
references.pmid: 19959030
references.citation: PLoS Genet. 2011 Apr;7(4):e1002042
references.pmid: 21533183
references.citation: Am J Surg Pathol. 2006 Aug;30(8):962-8
references.pmid: 16861966
references.citation: Science. 1990 Nov 30;250(4985):1233-8
references.pmid: 1978757
references.citation: Cancer Res. 2008 Aug 15;68(16):6587-97
references.pmid: 18701482
references.citation: Am J Physiol Cell Physiol. 2005 Mar;288(3):C494-506
references.pmid: 15692148
references.citation: J Pathol. 2009 Mar;217(4):469-82
references.pmid: 19148905
references.citation: Oncogene. 2014 May 22;33(21):2728-36
references.pmid: 23770857
references.citation: Br J Cancer. 2003 Jul 21;89(2):327-32
references.pmid: 12865925
references.citation: Genome Biol. 2004;5(3):214
references.pmid: 15003112
references.citation: J Proteome Res. 2013 Feb 1;12(2):605-14
references.pmid: 23214712
references.citation: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5813-8
references.pmid: 12724530
references.citation: Cancer Lett. 2008 Sep 18;268(2):187-201
references.pmid: 18482795
references.citation: J Cancer Res Clin Oncol. 2008 Oct;134(10):1097-103
references.pmid: 18386058
references.citation: PLoS Genet. 2014 Jan;10 (1):e1004107
references.pmid: 24453992
references.citation: BMC Med Genet. 2013 Sep 11;14:89
references.pmid: 24024685
references.citation: Traffic. 2010 Mar;11(3):361-82
references.pmid: 20070607
references.citation: J Cell Biol. 2010 Nov 1;191(3):615-29
references.pmid: 21041450
references.citation: Nat Commun. 2013;4:1831
references.pmid: 23652019
references.citation: Int J Cancer. 1981 Oct 15;28(4):409-15
references.pmid: 7309287
references.citation: Cancer Cell. 2012 Oct 16;22(4):536-46
references.pmid: 23079662
references.citation: Cancer Res. 1994 Jun 1;54(11):2869-72
references.pmid: 8187070
references.citation: Biochem J. 2004 Oct 15;383(Pt 2):237-48
references.pmid: 15242332
references.citation: Cell Metab. 2008 Oct;8(4):310-7
references.pmid: 18840361
references.citation: Mol Cancer Ther. 2011 Apr;10(4):697-707
references.pmid: 21447712
references.citation: J Endocrinol Invest. 2013 Mar;36(3):204-8
references.pmid: 23404184
references.citation: Nat Rev Mol Cell Biol. 2013 Feb;14(2):98-112
references.pmid: 23340574
references.citation: Toxicol Lett. 1985 Feb-Mar;24(2-3):119-24
references.pmid: 3983963
references.citation: Science. 2001 Sep 28;293(5539):2449-52
references.pmid: 11498544
references.citation: Trends Cell Biol. 2010 Apr;20(4):177-86
references.pmid: 20153650
references.citation: Pediatr Dev Pathol. 2012;15(1 Suppl):211-38
references.pmid: 22420729
references.citation: Pharmacol Rev. 2002 Sep;54(3):431-67
references.pmid: 12223531
references.citation: FEBS J. 2013 Sep;280(17):4323-34
references.pmid: 23822136
references.citation: Genes Dev. 2004 Nov 1;18(21):2614-26
references.pmid: 15489287
references.citation: Oncotarget. 2011 Apr;2(4):305-12
references.pmid: 21471610
references.citation: Cell. 2008 Jan 11;132(1):113-24
references.pmid: 18191225
references.citation: Growth Horm IGF Res. 2001 Oct;11(5):289-97
references.pmid: 11735247
references.citation: Nat Cell Biol. 2009 Jul;11(7):789-91
references.pmid: 19568263
references.citation: Cancer Lett. 2009 Jul 8;279(2):126-36
references.pmid: 19008039
references.citation: Biochimie. 2014 Dec;107 Pt B:188-202
references.pmid: 25241255
references.citation: Nat Genet. 1993 Feb;3(2):113-7
references.pmid: 8098985
references.citation: J Cell Mol Med. 2012 Jul;16(7):1377-91
references.pmid: 22225829
references.citation: J Cell Biochem. 2012 Jan;113(1):322-8
references.pmid: 21913217
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8655-9
references.pmid: 7567992
references.citation: Cancer Genet. 2012 May;205(5):232-41
references.pmid: 22682622
references.citation: Int J Cancer. 2010 Jan 15;126(2):426-36
references.pmid: 19609943
references.citation: PLoS One. 2010 Nov 30;5(11):e14157
references.pmid: 21152401
references.citation: EMBO J. 1998 May 15;17 (10 ):2855-64
references.pmid: 9582279
references.citation: PLoS One. 2014 Jan 10;9(1):e84618
references.pmid: 24427291
references.citation: FASEB J. 2007 Jul;21(9):2195-204
references.pmid: 17360850
references.citation: Nucleic Acids Res. 2011 Apr;39(7):2727-41
references.pmid: 21148147
references.citation: Trends Mol Med. 2012 Oct;18(10):599-606
references.pmid: 22877884
references.citation: Nature. 1992 Mar 19;356(6366):215-21
references.pmid: 1552940
references.citation: Oncogene. 2007 Sep 27;26(44):6442-7
references.pmid: 17452975
references.citation: Cell. 2012 Aug 17;150(4):752-63
references.pmid: 22901807
references.citation: Genes Dev. 2014 Jul 15;28(14 ):1578-91
references.pmid: 25030697
references.citation: J Biol Chem. 2011 Apr 15;286(15):12820-4
references.pmid: 21343302
references.citation: Oncogene. 2008 Mar 27;27(14 ):2004-14
references.pmid: 17922034
references.citation: Biostatistics. 2003 Apr;4(2):249-64
references.pmid: 12925520
references.citation: Mol Biol Cell. 2011 Apr 15;22(8):1409-19
references.pmid: 21346196