Annexin A3 Knockdown Suppresses Lung Adenocarcinoma.

Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin.

TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression.

Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax were significantly up-regulated while Bcl-2 was down-regulated. Moreover, coincident results were shown by immunohistochemistry in tumors from nude mice. TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation of P38, but had no effect on IκBα and ERK pathway. Taken together, TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis and therapy.

p62 Expression in primary carcinomas of the digestive system.

AIM: To characterize p62 expression and define the relationship between p62 expression and cell proliferation in primary carcinomas of the digestive system. METHODS: p62 expression was characterized in surgically resected tumor specimens from 60 patients with primary carcinomas of the digestive tract (including 22 esophageal carcinomas, 17 gastric carcinomas, and 21 colorectal carcinomas) and 40 patients with hepatocellular carcinoma (HCC) by immunohistochemistry (IHC). The cell proliferation was determined by IHC of Ki-67 in 40 patients with HCC. RESULTS: Twenty-two cases of esophageal carcinoma were histopathologically diagnosed as squamous cell carcinoma. We combined the gastric and colorectal carcinomas based on the equivalent histology. The 38 tumors in the combined groups, consisted of 17 well-differentiated, eight moderately differentiated, nine poorly differentiated carcinomas, and four mucinous adenocarcinomas. According to the criteria of Edmondson and Steiner, 40 patients with HCC were graded (2 grade I, 17 grade II and 21 grade III). p62 expression in primary carcinomas of the gastrointestinal tract (60/60,100%) was higher than that (27/40, 67.5%) of HCC (P<0.01, chi(2) = 19.63). High expression levels of p62 were positively correlated with histological grades in gastric and colorectal carcinomas (P<0.0001) and inversely associated with those in HCC (P = 0.0322). No significant correlations were observed for esophageal carcinomas (P = 0.8246). p62 expression was also detected in the cytoplasm of morphologically normal columnar epithelial cells adjacent to the cancer foci of gastric and colorectal carcinomas. In 40 HCC specimens, the mean Ki-67 labeling index (LI) was (19.6+/-16.0)%. It was (28.3+/-18.73)% in 12 cases with high p62 expression (+++), (7.53+/-14.83)% in 13 cases without p62 expression(-). Patients with a high p62 expression showed a significantly higher level of Ki-67 staining than those without p62 expression (P<0.05, t = 2.069). CONCLUSION: p62 expression is common in carcinomas of the digestive system and higher in carcinomas of the gastrointestinal tract than in primary HCC. p62 is a cellular differentiation-related protein. Cancer cells with a high p62 expression exhibited highgrowth fractions in HCC.