Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells.
OBJECTIVE
Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC.


METHODS
We analyzed the functional implications of dysadherin on cancer stemness by modification of the dysadherin gene in HCC cell lines.


RESULTS
The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSCs, including anti-apoptosis, their sphere-forming ability, side population phenotype, and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties.


CONCLUSIONS
These results show that dysadherin give rise to properties of CSC in HCC. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies.
Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea.
Jeong-Ran
JR
Park
Ran-Ju
RJ
Kim
Yoo-Kyung
YK
Lee
Soo-Rim
SR
Kim
Kyung-Jin
KJ
Roh
Seung Hyun
SH
Oh
Gu
G
Kong
Kyung-Sun
KS
Kang
Jeong-Seok
JS
Nam
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D007473:Ion Channels; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000502:physiology*; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular; D014162:Transfection; D014410:Tumor Stem Cell Assay
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm