Role of zonula occludens in gastrointestinal and liver cancers

Table 1 Expression of zonula occludens proteins in gastric, colon and liver cancers

Ref.	ZO-protein	Specimen and methods	Observation	Potential clinical relevance
Resnick et al[35]	ZO-1	Tissue sample by microarray staining	Increased expression in gastric intestinal-type adenocarcinoma while Reduced expression in diffuse gastric cancer	Associated with tumor differentiation
Kimura et al[36]	ZO-1	Tissue sample by immunohistochemistry	Reduced expression in poorly differentiated gastric adenocarcinoma	Correlated with tumor differentiation
Lee et al[37]	ZO-1	Tissue sample by immunohistochemistry	Reduced expression in diffuse gastric cancer	Associated with tumor differentiation
Ohtani et al[38]	ZO-1	Tissue sample by immunohistochemistry	Reduced expression in undifferentiated-type gastric adenocarcinoma	Associated with reduced overall survival
Zhu et al[39]	ZO-1	Tissue sample by microarray staining	Increased expression in gastrointestinal stromal tumor	Positively correlated with longer survival
Wang et al[41]	ZONAB	Tissue sample by western blotting and immunofluorescence	Increased expression in gastric cancer tissue	Knockdown of ZONAB by siRNA inhibited cyclin D1 mediated cell invasion and enhanced chemosensitivity of 5-fluorouracil
	ZO-2 and ZO-3			Not studied in gastric cancer patients
Kaihara et al[47]	ZO-1	Tissue sample by immunohistochemistry	Reduced expression in primary colorectal cancer	Reduced expression is attributed by tyrosine phosphorylation of ZO-1 and is required for dedifferentiation of glandular structure in CRC
Resnick et al[48]	ZO-1	Tissue sample by microarray staining	Reduced expression in colon cancer	Low expression is correlated with high tumor grade
Jeong et al[49]	ZO-1	Tissue sample by immunohistochemistry	Reduced expression in colon adenocarcinoma	Reduced expression is correlated with tumor cell differentiation
Mees et al[50]	ZO-1	Tissue sample by immunofluorescence	No difference in expression between colorectal carcinoma, adjoining intraepithelial neoplasia, and normal mucosa	Unknown
Orbán et al[72]	ZO-1	Tissue sample by PCR and immunohistochemistry	Reduced mRNA and protein expression in primary HCC; Increased protein expression in secondary colorectal liver metastasis tissue	Differential expression of ZO-1 is associated with distinct histological features in these tumors
Liu et al[51]	ZONAB	Tissue sample by immunohistochemistry	Increased expression in CRC	Increased expression is correlated with invasion, degree of differentiation, and colorectal metastasis
	ZO-2 and ZO-3			Not studied in colorectal cancer patients
Zhang et al[73]	ZO-1	Tissue sample by PCR and western blotting	Reduced mRNA and protein expression in HCC	Overexpression of ZO-1 inhibited HepG2 cell proliferation
Nagai et al[74]	ZO-1	Tissue sample by PCR	Reduced mRNA expression in HCC	Reduced expression is correlated with shorter overall survival and poor prognosis in HCC patients
Ram et al[75]	ZO-1	Tissue sample by immunohistochemistry; Plasma sample by ELISA	Reduced expression in HCC; Increased plasma concentration in HCC	Associated with inflammation and poor clinical outcome in HCC patients
Ram et al[76]	ZO-1	Tissue sample by western blotting	Reduced expression in HCC	Associated with inflammation and disease pathogenesis in DEN and NMOR induced HCC
Yasen et al[81]	ZONAB	Tissue sample by immunohistochemistry	Increased expression in HCC liver tissue	Nuclear staining of ZONAB is correlated with poor prognosis in HCC patients
	ZO-2 and ZO-3			Not studied in HCC patients

CRC: Colorectal cancer; DEN: Diethylnitrosamine; NMOR: N-nitrosomorpholine; HCC: Hepatocellular carcinoma; ZO-1: Zonula occludens-1; ZO-2: Zonula occludens-2; ZO-3: Zonula occludens-3; ZONAB: Zonula occludens-1 associated nucleic acid binding protein.