Tumor-Suppressive Functions of Leucine Zipper Transcription Factor–Like 1

Abstract

Human leucine zipper transcription factor-like 1 (LZTFL1) is a novel gene with unknown biological functions. It is located in the chromosome region 3p21.3, a hotspot for tumor suppressor genes. To understand the biological functions of LZTFL1, we surveyed the expression level of LZTFL1 in tumor and normal samples in tissue microarrays and a clinical archive of 84 gastric cancer specimens using immunohistochemistry. We found that LZTFL1 is expressed highly in the epithelial cells of normal tissues and is significantly downregulated in the corresponding tumor samples. The expression level of LZTFL1 correlated significantly with the survival outcomes of the patients and had significant inverse correlation with tumor metastasis. Overexpression of LZTFL1 in tumor cells inhibited anchorage-independent cell growth and cell migration in vitro and repressed tumor growth in vivo. Furthermore, we show that LZTFL1 expression is upregulated on epithelial cell differentiation and is graded along the crypt-villus axis of the intestine, with weakest expression level in the proliferative zone of the crypt and highest expression level at the apex of the differentiation zone in the villus. Expression of LZTFL1 overlaps with that of E-cadherin at the plasma membrane. Our results indicate that LZTFL1 is a tumor suppressor and that loss of LZTFL1 expression has significant clinical outcomes. LZTFL1 expression may serve as an independent prognostic marker for survival outcome of gastric cancer patients. We propose that LZTFL1 may inhibit tumorigenesis by stabilizing E-cadherin-mediated adherens junction formation and promoting epithelial cell differentiation. Cancer Res; 70(7); 2942-50. ©2010 AACR.

Leucine zipper transcription factor-like 1 expression in gastric cancer and its relationship to relative adhesion molecule

“…Wang et al have suggested that cytoplasmic LZTFL1 and E-cadherin inhibit β-catenin nuclear transport and EMT processes in GC cells, thereby inhibiting their invasion and metastasis [7]. This is in agreement with the results obtained in the present study, in which LZTFL1 protein expression was positively correlated with E-cadherin, and negatively correlated with β-catenin.…”

“…The results obtained in this study showed that LZTFL1 in epithelial cells of normal tissues was highly expressed, but was lowly expressed in samples of corresponding invasive cancer group [7]. LZTFL1 expression is of prognostic significance in GC.…”

“…LZTFL1 is a 299 amino acid-residue tumor suppressor molecule of molecular weight 34.6KD [7]. It is expressed in low amounts in multiple malignant tumors, and is correlated with gastric, NSCLC and liver cancers [8,9].…”

Clinical significance of apoptosis-associated speck-like protein containing a caspase recruitment domain in oral squamous cell carcinoma

“…The percentage of ASCpositive cells in carcinoma (epithelial) cells was calculated in the printed image (300 dot per inch). We classified the sections into three grades (ASC score 1; positive cells 33%, score 2; 34%-66%, and score 3; 67%-100%) according to the modified method of Wei et al 20 Each section was examined by two independent examiners (H. Ko and H. Ai) and there was no disagreement in the final ASC score.…”

Monitoring endoplasmic reticulum stress responsive mRNAs by RNA sequencing

“…Although we expected to see well-known genes for cell death in Group II, we could not find such genes except for NDRG1 (Stein et al, 2004). However, we were able to identify LZTFL1, a known transcription factor and tumor suppressor gene related to growth arrest (Wei et al, 2010), as a novel ER stress responsive gene from this group. Contrary to the expectation, several genes from the group are known to function in UPR and ERAD (marked with *).…”