Hsp60 exerts a tumor suppressor function by inducing cell differentiation and inhibiting invasion in hepatocellular carcinoma.
Heat shock protein 60 (Hsp60), a typical mitochondrial chaperone, is associated with progression of various cancers. However, its expression and significance in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, the mRNA and protein expression of Hsp60 in HCC tissues were detected by quantitative RT-PCR (n=24), western blot (n=7), and immunohistochemical staining (n=295), respectively. The correlation between Hsp60 expression and clinicopathological characteristics of HCC patient was also analyzed. Meanwhile, the influence of Hsp60 on malignant phenotype of HCC cells was further investigated. We found that expression of Hsp60 was significantly downregulated in HCC tissues compared to peritumor tissues. Hsp60 expression was significantly correlated with serum alpha -foetoprotein (AFP) level and tumor differentiation grade. Moreover, high Hsp60 expression cancer/pericancer (C/P) ratio was associated with a better overall survival rate (P=0.035, n=295). The prognostic implication of Hsp60 in HCC was further confirmed in another cohort of 107 HCC patients (P=0.027). Up-regulation of Hsp60 remarkably induced the cell differentiation and inhibited the invasive potential of HCC in vitro and in vivo. Intriguingly, the down-regulation of Hsp60 significantly impaired mitochondrial biogenesis. Although more data are required to clarify the underling mechanism responsible for function of Hsp60, our results suggested that the effect of Hsp60 on differentiation and invasion of HCC cells might be associated with mitochondrial biogenesis. Collectively, our findings indicated that Hsp60 exerted a tumor suppressor function, and might serve as a potential therapeutic target in the treatment of HCC.
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Jing
J
Zhang
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xingchun
X
Zhou
Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Hulin
H
Chang
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xiaojun
X
Huang
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xu
X
Guo
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xiaohong
X
Du
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Siyuan
S
Tian
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Lexiao
L
Wang
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Yinghua
Y
Lyv
Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Peng
P
Yuan
State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Jinliang
J
Xing
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D001678:Organelle Biogenesis; D010641:Phenotype; D011379:Prognosis; D034622:RNA Interference; D015854:Up-Regulation
D018834:Chaperonin 60; C060293:HSPD1 protein, human; D024101:Mitochondrial Proteins
Hsp60; differentiation; hepatocellular carcinoma; invasion; mitochondrial biogenesis
Cancer Lett. 2005 Nov 18;229(2):245-52
16112431
Leuk Res. 2005 Sep;29(9):1049-58
16038731
Eur J Haematol. 2003 Aug;71(2):100-8
12890148
Cancer Sci. 2007 Feb;98(2):201-13
17233837
PLoS One. 2013 Jul 29;8(7):e70324
23922981
Cancer Res. 2014 Feb 1;74(3):954-63
24351292
Cancer Biol Ther. 2008 Jun;7(6):801-9
18497565
World J Gastroenterol. 2005 Apr 14;11(14):2072-9
15810071
Gastroenterology. 2004 Nov;127(5 Suppl 1):S5-S16
15508102
PLoS One. 2012;7(12):e51703
23272146
Eur J Gastroenterol Hepatol. 2008 Feb;20(2):104-10
18188029
Cancer Lett. 2004 Jan 8;203(1):25-33
14670614
Anticancer Res. 2000 Mar-Apr;20(2A):825-31
10810361
J Biol Chem. 2008 Feb 22;283(8):5188-94
18086682
Eur J Histochem. 2003;47(2):105-10
12777205
Clin Exp Metastasis. 1985 Oct-Dec;3(4):257-79
3907917
Cell Res. 2007 Apr;17 (4):363-73
17372612
Int J Cancer. 2015 Mar 15;136(6):E496-507
25130271
Annu Rev Biochem. 1993;62:349-84
8102520
J Biol Chem. 2015 May 1;290(18):11611-22
25792736
J Natl Cancer Inst. 2008 Aug 6;100(15):1104-12
18664653
Proteomics Clin Appl. 2007 Mar;1(3):336-42
21136683
Curr Protein Pept Sci. 2001 Sep;2(3):227-44
12369934
Hepatology. 2014 Apr;59(4):1459-70
24214128
BMC Cancer. 2005 Oct 28;5:139
16253146
Pathol Res Pract. 2005;201(12 ):777-89
16308103
Circulation. 2002 Feb 26;105(8):1012-7
11864934
Anticancer Res. 2009 Dec;29(12 ):5057-63
20044617
Yonsei Med J. 2009 Jun 30;50(3):399-406
19568603
Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6603-8
21467224
Biochem J. 2005 Oct 15;391(Pt 2):185-90
15957980
Nature. 1989 Feb 16;337(6208):620-5
2645524
Oncotarget. 2015 Aug 28;6(25):21636-44
26046304
Gut. 2004 Apr;53(4):581-6
15016755
Front Oncol. 2011 Nov 10;1:37
22649762
Dig Dis Sci. 2013 Sep;58(9):2721-8
23703450
Gastroenterology. 2007 Jun;132(7):2557-76
17570226
Nat Rev Urol. 2015 Jan;12(1):26-36
25512207
Electrophoresis. 1997 Dec;18(15):2832-41
9504817
Expert Rev Proteomics. 2005 Aug;2(4):589-601
16097891
J Clin Pathol. 2008 Jan;61(1):49-58
17412869
Anticancer Res. 2003 Mar-Apr;23(2B):1325-31
12820390
Hepatology. 2011 May;53(5):1558-69
21520171
PLoS One. 2014 Sep 10;9(9):e107507
25207654
Urology. 2010 Oct;76(4):1017.e1-6
20708221