TSG101, identified by screening a cancer cDNA library and soft agar assay, promotes cell proliferation in human lung cancer

Abstract

Understanding the genesis and development of tumors is an essential component in cancer research. It is of interest to discover unknown genes that are responsible for cellular transformation. A cDNA library of a highly metastatic lung adenocarcinoma cell line was constructed. This library was introduced into the NIH3T3 mouse embryonic fibroblast cell line to screen for cDNAs that increase anchorage-independent colony formation in soft agar. The expression of TSG101 in lung cancer cell lines and specimens was confirmed using reverse transcription-polymerase chain reaction. The level of TSG101 protein in transfected A549 cells was determined by western blotting. Cell-cycle distribution was analyzed using a FACStar Plus flow cytometer. One of the candidate cDNAs that increases anchorage-independent colony formation was shown to correspond to the TSG101 cDNA sequence. Levels of TSG101 mRNA were higher in lung cancer cell lines and specimens compared to matched normal lung tissues. Ectopic expression of TSG101 in the A549 lung adenocarcinoma cell line increased the numbers of cells in S phase, suggesting an increased cell proliferation rate. These results indicate that TSG101 may induce the malignant phenotype of cells.

The role of the endosomal sorting complexes required for transport (ESCRT) in tumorigenesis

“…Moreover, Tsg101 does promote growth in NIH3T3 fibroblasts as well as in lung cancer cells (Liu et al, 2010). One study, using conditional Cre-mediated deletion of Tsg101 in mouse embryonic fibroblasts, reports the post-transcriptional down-regulation of the EGFR upon Tsg101 depletion and induction of autophagy prior to cell death (Morris et al, 2012).…”

“…Regarding the expression levels of Tsg101 in lung cancer, different results have been reported. In one study, Tsg101 was found to be up-regulated in 15 lung cancer cell lines and five lung cancer tissue specimens (Liu et al, 2010). Other studies described Tsg101 levels to be decreased in different human lung cancer samples (Cai et al, 2008; Lu et al, 2007); reviewed in (Jiang et al, 2013).…”

Tumor Susceptibility Gene 101 Mediates Anoikis Resistance of Metastatic Thyroid Cancer Cells

“…Therefore, we hypothesize that endocytosis of death receptors has the potential to be a mechanism by which cancer cells resist anoikis. TSG101 is involved in vesicular biogenesis, endocytosis, membrane trafficking and receptor recycling (33). Moreover, defective mutations of TSG101 had been shown to impair trafficking of endocytosed epidermal growth factor (EGF) receptors to lysosomes, which resulted in decreased degradation of EGF receptors and prolonged mitogenic signaling in cells (32).…”

Identification of genes showing differential expression profile associated with growth rate in skeletal muscle tissue of Landrace weanling pig

“…The EEF1A2, TSG101 and TTN identified as upregulated genes in high-growth group have been reported to be involved in myotube survival and protection from apoptosis (Ruest et al 2002), cell growth and maintenance of genomic stability (Krempler et al 2002;Liu et al 2010), and Figure 2. Western blot analysis of EEF1A2, TSG101, ATP5B, ATP5C1, COQ3, HADHA, MYH1 and MYH7 expression levels in skeletal muscle tissues of high-growth (high) and low-growth groups (low).…”