HAb18G/CD147 inhibits starvation-induced autophagy in human hepatoma cell SMMC7721 with an involvement of Beclin 1 down-regulation.
HAb18G/CD147, a transmembrane glycoprotein highly expressed in various types of malignant cells, mainly functions as an inducer of matrix metalloproteinases to promote tumor growth, invasion and metastasis. However, whether there are other mechanisms underlying the role of HAb18G/CD147 in tumor progression remains to be elucidated. In this study, we investigated the functional effects of HAb18G/CD147 on autophagy in hepatoma cell line SMMC7721 using immunofluorescence staining, Western blot and transmission electronmicroscopy. Our data showed that specific small interference RNA (siRNA) considerably down-regulated the expression of HAb18G/CD147 in SMMC7721 cells at both messenger RNA (mRNA) and protein levels. The down-regulation of HAb18G/CD147 significantly promoted starvation-induced autophagy in a dose-dependent manner. Using trypan blue exclusion assay, we found that HAb18G/CD147 notably enhanced the survival of SMMC7721 cells through inhibiting starvation-induced autophagy. In addition, we demonstrated that HAb18G/CD147 down-regulated the expression of autophagy-regulating protein Beclin 1 in SMMC7721 cells. Furthermore, our data indicated that HAb18G siRNA-transfected SMMC7721 cells had a significantly decreased level of phosphorylated serine/threonine protein kinase B (pAkt) and the expression of Beclin 1 was inversely associated with the level of pAkt, suggesting that the Class I phosphatidylinositol 3 kinase-Akt pathway may be involved in the down-regulation of Beclin 1 by HAb18G/CD147. Overall, we provide the first experimental evidence to show that HAb18G/CD147 may play an important role in the inhibitory regulation of autophagy. Therefore, our data suggest a new molecular mechanism for HAb18G-mediated hepatoma progression.
Gou
Xingchun
X
Department of Cell Biology & Cell Engineering Research Center & State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, 710032.
Ru
Qiang
Q
Zhang
Hongxin
H
Chen
Yanke
Y
Li
Ling
L
Yang
Hushan
H
Xing
Jinliang
J
Chen
Zhinan
Z
D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017603:Signal Detection, Psychological
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051926:Basigin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt