CEACAM1 long cytoplasmic domain isoform is associated with invasion and recurrence of hepatocellular carcinoma.

Abstract

BACKGROUND:

The two isoforms of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), 1 with a long cytoplasmic domain (CEACAM1-L) and 1 with a short (CEACAM1-S), are involved in different signaling pathways. β2-spectrin (β2SP) is an adaptor protein that plays critical roles in the proper control of Smad access to activate receptors involved in regulation of TGF-β signaling. In this study, we examined the association between CEACAM1 isoform balance and hepatocellular carcinoma (HCC) malignant potential and investigated the possibility of a molecular interaction between CEACAM1 and β2SP.

METHODS:

Immunohistochemical analysis was carried out with CEACAM1-L or CEACAM1-S antibodies on 154 HCC tissues to correlate with the factors of malignancy. Invasion assay was performed for the effect of CEACAM1 expression on HCC cell lines. Moreover, immunohistochemical analysis and immunoprecipitation analysis were performed to investigate the association between CEACAM1 isoform balance and β2SP.

RESULTS:

In immunohistochemical analysis, CEACAM1-L expression dominance was a risk factor for HCC recurrence (p = 0.04) and was significantly associated with a shorter survival compared with CEACAM1-S expression dominance. Invasion assay indicated that CEACAM1-4L-transfected HLF and PLC/PRF/5 cells showed significantly increased invasion (p < 0.0001) and CEACAM1-4S-transfected HLF cells showed significantly decreased invasion. Immunohistochemical analysis of β2SP suggested that the HCCs with CEACAM1-L-dominant expression were more strongly stained with β2SP than the HCCs with CEACAM1-S-dominant expression (p = 0.013), and coprecipitation assays indicated that CEACAM1-L could bind to β2SP.

CONCLUSIONS:

CEACAM1-L may enhance the HCC invasiveness through an interaction with β2SP and subsequent effects on TGF-β signaling.

• Authors: Shigehisa Kiriyama, Shozo Yokoyama, Masaki Ueno, Shinya Hayami, Junji Ieda, Naoyuki Yamamoto, Shunsuke Yamaguchi, Yasuyuki Mitani, Yasushi Nakamura, Masaji Tani, Lopa Mishra, John E Shively, Hiroki Yamaue
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 21 Suppl 4 Pg. S505-14 (Dec 2014) ISSN: 1534-4681 [Electronic] United States
• PMID: 24390710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• CD66 antigens
• Cell Adhesion Molecules
• Protein Isoforms
• SPTBN1 protein, human
• Smad3 Protein
• Transforming Growth Factor beta
• Spectrin

Topics

• Aged
• Antigens, CD (analysis, genetics, metabolism)
• Apoptosis
• Carcinoma, Hepatocellular (chemistry, genetics, pathology)
• Cell Adhesion Molecules (analysis, genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Female
• Humans
• Liver Neoplasms (chemistry, genetics, pathology)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local (chemistry)
• Protein Isoforms (analysis)
• Retrospective Studies
• Signal Transduction
• Smad3 Protein (metabolism)
• Spectrin (analysis, metabolism)
• Survival Rate
• Transfection
• Transforming Growth Factor beta (metabolism)