Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo.
BACKGROUND
Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in hepatocellular carcinoma (HCC) remain unknown.


METHODS
Quantitative reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of HSF1, and its correlation with clinicopathologic parameters and the prognosis for patients with HCC were analyzed. In addition, the biologic function and molecular mechanisms of HSF1 in HCC were investigated in vitro and in vivo.


RESULTS
HSF1 levels were elevated predominantly in HCC, especially in venous emboli from HCC (P < .05), and high expression levels of HSF1 were correlated significantly with multiple nodules, venous invasion, absence of capsular formation, and high Edmondson-Steiner grade as well as poor overall survival and disease-free survival in patients with HCC (P < .05). Multivariate Cox regression analysis revealed that high HSF1 expression was an independent prognostic factor for overall survival in patients with HCC (relative risk, 4.874; P < .001). Finally, HSF1 was capable of promoting HCC cell migration and invasion in vitro and in vivo by facilitating the expression and phosphorylation of heat shock protein 27.


CONCLUSIONS
Collectively, the current findings suggested that HSF1 may serve as a novel prognostic marker and therapeutic target for HCC.
Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Feng
F
Fang
Ruimin
R
Chang
Lianyue
L
Yang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors