ABSTRACT
Objective To investigate the expressions of large tumor suppressor kinase 1 (LATS1) and large tumor suppressor kinase 2 (LATS2) proteins in gastric cancer tissues, and to explore the correlation between expressions of LATS1 and LATS2 proteins and the occurrence and development of gastric cancer. Methods A total of 93 gastric cancer paraffin tissues and the corresponding adjacent gastric normal mucosa in the Department of Pathology in Baotou Cancer Hospital from September 2008 to June 2010 were collected. The immunohistochemistry was used to detect the expressions of LATS1 and LATS2 proteins in gastric cancer and adjacent normal tissues. The differences of the expressions of LATS1 and LATS2 proteins in gastric cancer and adjacent normal tissues were compared by usingχ2 test. The relationship between the expressions of LATS1 and LATS2 proteins and the clinicopathological features was also analyzed. Results In gastric cancer tissues, LATS1 was negatively expressed in 54 cases (58.1％), weakly positive expressed in 15 cases (16.1％), moderately positive expressed in 16 cases (17.2％), and strongly positive expressed in 8 cases (8.6％);in adjacent normal tissues, LATS1 was negatively expressed in 17 cases (18.3％), weakly positive expressed in 16 cases (17.2％), moderately positive expressed in 31 cases (33.3％), and strongly positive expressed in 29 cases (31.2％). The positive expression rate of LATS1 in gastric cancer tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (χ2=37.460, P<0.01). In gastric cancer tissues, LATS2 was negatively expressed in 28 cases (30.1％), weakly positive expressed in 17 cases (18.3％), moderately positive expressed in 33 cases (35.5％), strongly positive expressed in 15 cases (16.1％);in adjacent normal tissues, LATS2 was negatively expressed in 5 cases (5.4％), weakly positive expressed in 7 cases (7.5％), moderately positive expressed in 32 cases (34.4％), strongly positive expressed in 49 cases (52.7％). The positive expression rate of LATS2 in gastric cancer tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (χ2=38.275, P<0.01). The expressions of LATS1 and LATS2 were not related to patients'age, gender, lymph node metastasis, degree of differentiation and tumor diameter (all P>0.05). Conclusion LATS1 and LATS2 proteins may be involved in the occurrence of gastric cancer and have the inhibiting effect on the occurrence and development of gastric cancer.
ABSTRACT
Large tumor suppressor kinase 1 (LATS1) and LATS2 are the kinases found in recent years which can inhibit the tumor development. They are highly homologous and overlap in function. LATS1 and LATS2 proteins have been confirmed to be associated with the occurrence of multiple malignancies, including soft tissue sarcoma, leukemia, astrocytoma, breast cancer, prostate cancer, lung cancer, liver cancer, esophageal cancer, etc. Studies have shown that LATS has more extensive biological functions, such as regulating gene transcription and cell cycle checkpoint, inducing apoptosis, inhibiting cell migration, maintaining genetic stability and regulating organ size, and loss of any one can cause a variety of biological changes. So insighting into the structure and mechanism of LATS1 and LATS2 is the key to understanding the occurrence and development of tumors. The discovery of LATS gene and the structure, expression, target and function of LATS protein are summarized in this paper.
ABSTRACT
Objective To explore the role of Hippo pathway in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD),and find potential targets for drug therapy.Methods By means of immunofluorescence staining,Western blotting,Real-time PCR,the differences of sublocalization,expression and phosphorylation level about Hippo pathway molecules in Han:SPRD (cy/+) and ADPKD patients compared with the control were observed.Knockdown Yes kinaseassociated protein (YAP),transcriptional coactivator with PDZ binding motif (TAZ) and large tumor suppressor kinase1 (LATS1) in cystic lining epithelium cell line WT9-12 were took by siRNA interference,and then their effects on cell proliferation,apoptosis and cell cycle were assessed.Results In cystic lining epithelium of Han:SPRD(cy/+),decreased expression of LATS1 and increased expression of YAP were found compared with the control,and the immunofluorescence of YAP was distributed both in cytoplasm and nucleus,while distribution and expression level of TAZ were without significant variance.Abnormal mRNA expressions of Hippo pathway components in ADPKD patients were found (P ＜ 0.05).Down-regulation of LATS1 in WT9-12 cells could prohibit phosphorylation of YAP,and prompted proliferation and cell division.Knockdown YAP in WT9-12 cells could inhibited cell proliferation by arresting cell cycle in G0/G1 phase,but down-regulating TAZ showed no significant differences in proliferation and cell cycle.Conclusions Altered Hippo signaling exists in ADPKD,and YAP activation may be one leading cause of autosomal dominant polycystic kidney disease onset.In vitro,knockdown YAP in WT9-12 cells can inhibit cell proliferation by arresting cell cycle and depressing cell division,suggesting the expression level and activity of YAP are potential targets for ADPKD treatment.