title: The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma.
abstract: The molecular pathogenesis of hepatocellular carcinoma (HCC) is heterogeneous and extremely complex. Thus, for individual molecular targeted therapy, novel molecular markers are needed. The abnormal expression of the human homolog of Drosophila headcase (HECA homo) has been found in pancreatic, colorectal, and oral squamous cell carcinoma. Studies of oral squamous cell carcinoma have also demonstrated that the HECA homo protein can be negatively controlled by the Wnt-pathway and transcription factor 4 (TCF4) and can slow cell division by interacting with cyclins and CDKs. However, the role of HECA in HCC has not been reported elsewhere. Here, immunohistochemical analysis revealed that the downregulation of HECA homo protein occurred in 71.0% (66/93) of HCC cases and was positively correlated with a poorly differentiated grade, high serum AFP level, liver cirrhosis and large tumor size. The expression of HECA homo was detected in five live cell lines. In vitro, the overexpression of HECA homo in HepG2, Huh-7 and MHCC-97H cells could inhibit cell proliferation and colony formation and induce G1 phase arrest. In contrast, the downregulation of HECA homo could promote cell proliferation, colony formation and the cell cycle process. However, neither the overexpression nor downregulation of HECA homo in the three cell lines could affect cell migration or invasion. Collectively, HECA homo is regularly expressed in normal live cells, and the HECA homo protein level is heterogeneously altered in HCC, but the downregulation of HECA homo is more common and positively correlated with several malignant phenotypes. The HECA homo protein can slow cell proliferation to some extent primarily through its blocking effect on the cell cycle. Hence, the HECA homo protein may act as a tumor suppressor in HCC and might be a potential molecular marker for diagnostic classification and targeted therapy in HCC.
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Zhu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Han
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C445125:HECA protein, human; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins