Prefoldin 1 promotes EMT and lung cancer progression by suppressing cyclin A expression.
Prefoldin (PFDN) is a co-chaperone protein that is primarily known for its classic cytoplasmic functions in the folding of actin and tubulin monomers during cytoskeletal assembly. Here, we report a marked increase in prefoldin subunit 1 (PFDN1) levels during the transforming growth factor (TGF)-β1-mediated epithelial-mesenchymal transition (EMT) and in human lung tumor tissues. Interestingly, the nuclear localization of PFDN1 was also detected. These observations suggest that PFDN1 may be essential for important novel functions. Overexpression of PFDN1 induced EMT and cell invasion. In sharp contrast, knockdown of PFDN1 generated the opposite effects. Overexpression of PFDN1 was also found to induce lung tumor growth and metastasis. Further experiments showed that PFDN1 overexpression inhibits the expression of cyclin A. PFDN1 suppressed cyclin A expression by directly interacting with the cyclin A promoter at the transcriptional start site. Strikingly, cyclin A overexpression abolished the above PFDN1-mediated effects on the behavior of lung cancer cells, whereas cyclin A knockdown alone induced EMT and increased cell migration and invasion ability. This study reveals that the TGF-β1/PFDN1/cyclin A axis is essential for EMT induction and metastasis of lung cancer cells.
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
D
D
Wang
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
W
W
Shi
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Y
Y
Tang
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Y
Y
Liu
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
K
K
He
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Y
Y
Hu
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J
J
Li
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Y
Y
Yang
State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J
J
Song
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D056750:Cyclin A1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; C503745:CCNA1 protein, human; D056750:Cyclin A1; D018832:Molecular Chaperones; D053773:Transforming Growth Factor beta1; C112806:prefoldin
FEBS Lett. 2010 Nov 19;584(22):4646-54
20971111
Nat Commun. 2015 Sep 10;6:8230
26354229
Annu Rev Cell Dev Biol. 2011;27:347-76
21740232
Dev Biol. 2008 Jan 1;313(1):320-34
18062952
Cell Mol Life Sci. 2014 Dec;71(24):4881-94
24879294
EMBO J. 2002 Dec 2;21(23):6377-86
12456645
Int J Oncol. 2014 Jan;44(1):161-6
24212916
EMBO J. 2001 May 15;20(10):2376-86
11350926
J Biol Chem. 2013 Oct 25;288(43):31206-16
24022481
Asian Pac J Cancer Prev. 2013;14(2):915-21
23621261
Ann Surg Oncol. 2010 Nov;17(11):3030-6
20552408
J Cell Biol. 2012 Jan 9;196(1):147-62
22232705
Cancer Res. 2009 Sep 15;69(18):7180-7
19738073
Biol Cell. 2009 Sep 23;102(1):1-12
19566485
Cell Res. 2011 Feb;21(2):316-26
20820189
J Biol Chem. 2001 Dec 7;276(49):46562-7
11585818
Cancer Res. 2012 Oct 15;72 (20):5261-72
22896337
Open Biol. 2014 Jul;4(7):null
25008233
BMB Rep. 2008 Feb 29;41(2):158-63
18315953
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5490-4
8202514
Cell. 2011 Mar 4;144(5):646-74
21376230
Curr Opin Oncol. 2013 Jan;25(1):76-84
23197193
Carcinogenesis. 2015 Aug;36(8):914-24
25993989
Carcinogenesis. 2013 Aug;34(8):1764-72
23615405
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
24556840
Cancer Res. 1996 Jul 1;56(13):2881-5
8674032
Curr Biol. 1994 Feb 1;4(2):89-99
7953530
Cancer Invest. 2011 May;29(4):272-81
21345069
Cell. 1998 May 29;93(5):863-73
9630229
J Transl Med. 2013 Aug 01;11:182
23914742
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17368-73
24101513
Cell. 2000 Nov 10;103(4):621-32
11106732
Cancer Res. 2015 Apr 15;75(8):1580-91
25744716
Nat Rev Cancer. 2011 Mar;11(3):177-87
21326322
Cancer Res. 2015 Jul 15;75(14):2822-32
26018088
J Immunol. 2008 Jul 1;181(1):476-84
18566413
Cancer Res. 2013 May 15;73(10 ):3109-19
23492367
Cancer Res. 1999 Aug 15;59(16):4148-54
10463621
Oncogene. 1995 Apr 20;10(8):1501-9
7731704
PLoS One. 2012;7(7):e41891
22844532
Oncogene. 2001 Aug 9;20(35):4853-63
11521196
Pancreatology. 2005;5(4-5):370-9
15983444
Tissue Antigens. 2007 Feb;69(2):181-8
17257322
J Biol Chem. 2013 Jan 25;288(4):2179-89
23235160
Acta Med Okayama. 1996 Apr;50(2):73-7
8744932
PLoS Genet. 2013;9(9):e1003776
24068951
Oncogene. 2013 Feb 14;32(7):805-18
22508478
Clin Cancer Res. 2013 Oct 15;19(20):5686-98
23974006
Cancer Res. 2010 Oct 15;70(20):8127-37
20924103
CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30
26742998
Oncogene. 2006 Nov 23;25(55):7235-44
16799646
Cancer Metastasis Rev. 2009 Jun;28(1-2):15-33
19169796