Decreased TIP30 Expression Promotes Tumor Metastasis in Lung Cancer

Abstract

The HIV Tat-interacting protein (TIP30), also called CC3 or HTIP2, is encoded by Tip30, a putative tumorsuppressor gene located on human chromosome 11p15.1. In this study, we investigated the role of TIP30 in the progression and metastasis of lung cancer. TIP30 expression was analyzed in 206 paired lung cancers and adjacent non-tumor tissues, as well as in 70 matched lymph node metastases using a high-density tissue microarray. Results were compared with the clinicopathologic features of the patients from whom the tissues were taken. Low TIP30 expression levels were found in all 9 cases of small cell lung cancer and in 36.5% (72/197) of non-small cell lung cancer, which were correlated with lymph node metastasis in non-small cell lung cancer and with poor differentiation and advanced stage of tumor cells in squamous cell carcinoma. The immunostaining scores were significantly lower in the metastatic lesions than in the primary lesions. Down-regulation of TIP30 by a short hairpin RNA enhanced cell survival, migration, and invasion through Matrigel in vitro, and promoted lung metastasis and vascularization in nude mice. Further studies revealed that the downregulation of TIP30 enhanced the expression of osteopontin, as well as matrix metalloproteinase-2 and vascular endothelial growth factor. Our results suggest that the down-regulation of TIP30 promotes metastatic progression of lung cancer, hence it could serve as a potential target for the development of lung cancer therapies.

ALDH1A3 correlates with luminal phenotype in prostate cancer

“…BCR was defined as two consecutive increases post-operative prostate-specific antigen (PSA) 0.2 ng/mL or greater in serum. For the staining score system, 12 the percentage of positive tumor cells was determined by at least five areas at 400× magnification and assigned to one of the following five categories-0: <5%, 1: 5%-25%, 2: 25%-50%, 3: 50%-75%, and 4: >75%. The intensity of immunostaining was scored as follows-1: low, 2: moderate, and 3: strong.…”

Molecular and Genetic Aspects of Lung Cancer

“…The authors propose that TIP30 may function as a tumor suppressor gene and may play important roles in suppressing the progression and metastasis of lung cancer. These findings highlight TIP30 as a potential new therapeutic for metastatic lung cancer (88).…”

“…the study of tong et al (88) on TIP30 expression in paired cancerous and non-cancerous lung tissue suggests that TIP30 is a putative tumor suppressor gene with decreased expression in numerous cancers including melanoma, breast cancer, and colon cancer. TIP30 expression was decreased in a third of NSCLCs compared with normal controls, and reduced TIP30 expression correlated with lymph node metastasis.…”

TIP30 Directly Binds p53 Tumor Suppressor Protein In Vitro

“…The amino acid sequence of human TIP30 was later confirmed to be identical to that of human CC3 (Xiao et al, 1998). TIP30, which exhibits decreased expression in some cancer cells NicAmhlaoibh and Shtivelman, 2001;Shtivelman, 1997;Tong et al, 2009;Zhao et al, 2006), is a tumor suppressor with proapoptotic activity (El Omari et al, 2005;Xiao et al, 2000;Zhao et al, 2007) as well as with anti-metastatic Shtivelman, 1997;Tong et al, 2009;Xiao et al, 2000;Zhao et al, 2007) and angiogenesis-inhibiting (NicAmhlaoibh and Shtivelman, 2001) properties. TIP30 binds importin-β, which facilitates the cytoplasm-to-nuclear transport of proteins (El Omari et al, 2005;King and Shtivelman, 2004;Zhao et al, 2008), including HuR (Guttinger et al, 2004;Wang et al, 2004).…”