Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Abstract

Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma

“…We observed a strong decrease of 55.06% (38 of 69) and 66.66% (46 of 69) in LATS1and LATS2 mRNA expression respectively in NSCLC tissues as compared to normal. These results are quite comparable to those observed in NSCLC [24], Soft tissue sarcomas [12], breast cancers [20], astrocytomas [16], gliomas [25] colorectal cancers [26], gastric cancers [27] and ALL [18]. Since, LATS1 is reportedly involved in the control of proliferation, invasion, apoptosis and/or differentiation of various types of cells [28,29] we also compared the LATS1 mRNA expression with various clinicopathological characteristics.…”

“…However, in our study, a significant decrease in LATS1 and LATS2 mRNA expression was observed in NSCLC tissues with LATS1 and LATS2 hypermethylation respectively, than those without hypermethylation (P < 0.001) suggesting that hypermethylation of the promoter region down-regulates its expressionand is in consistence with the reports on ALL [18], breast cancers [20], astrocytomas [7], soft tissue sarcomas [12], colorectal cancers [26], and gastric cancers [27], which showed that hypermethylation of LATS1 and LATS2 genes was associated with a decreased mRNA expression.…”

“…Since, LATS1 is reportedly involved in the control of proliferation, invasion, apoptosis and/or differentiation of various types of cells [28,29] we also compared the LATS1 mRNA expression with various clinicopathological characteristics. Our study showed that LATS1 mRNA expression significantly correlated with positive lymph node status (P = 0.001) which is in agreement with the earlier reported studies [20,24,27]. In addition, tumor size was significantly associated with LATS1 expression (P = 0.015) and results are in concordance with those reported in breast cancer [20] but in contradiction with those reported in NSCLC [24].…”

MicroRNA-506 inhibits gastric cancer proliferation and invasion by directly targeting Yap1

“…The Hippo pathway plays an important role in tumorigenesis and tumor progression through the YAP-TEAD complex [27]. In recent years, the Hippo signaling pathway was shown to be involved in the development, progression, and metastasis of human GC [17,28]. Furthermore, Yap1 exhibits oncogenic activity in cancer via crosstalk with other signaling pathways, such as Wnt, RAF/MEK/ERK, Notch, and PTEN/PI3K/AKT [17,[29][30][31].…”

Comparative Analysis of Oct4 in Different Histological Subtypes of Esophageal Squamous Cell Carcinomas in Different Clinical Conditions

“…Further, in a study by Kim et al (2013) expressions for stem cell markers including Oct4 were inducible by treatment with H 2 O 2 of the human malignant mesothelial cell line. In a study by Zhou et al (2013) using human biopsy materials of gastric origin, the Hippo signalling pathway marker mRNAs including that of Oct4 exhibited an increasing tendency from cancerous tissue to normal gastric mucosa. And the mRNA expressions had a close correlation with lymphatic metastasis and tumor TNM staging.…”