In BMC Cancer this week, researchers in Taiwan say that both isoforms of the Tazarotene-induced gene 1 tumor supressor gene supress cell growth in human colon cancer cell lines. Although the B isoform of TIG1 is known to inhibit growth and invasion of cancer cells, not much is known about the A isoform, the researchers write. In this study, the team found that both TGI1 isoforms are expressed at high levels in normal prostate tissue, and are downregulated in colon cancer cell lines. In particular, upregulation of the G protein-coupled receptor kinase 5 in cancer tissues supported the tumor-suppressing action of the TGI1A isoform. "Knockdown of GRK5 expression alleviated TIG1A-induced growth suppression of HCT116 cells, suggesting that GRK5 mediates cell growth suppression by TIG1A," the authors write. "Thus, TIG1 may participate in the downregulation of G protein-coupled signaling by upregulating GRK5 expression."
Also in BMC Cancer this week, researchers at Harvard Medical School report that genes associated with prognosis after surgery for malignant pleural mesothelioma promote the survival of tumor cells in vitro. The authors had previously described a test to predict clinical outcomes in mesothelioma patients after surgery — ARHGDIA, COBLL1, PKM2, and TM4SF1. In order to determine if any of these four genes have a cancer-relevant phenotype, the researchers conducted a high-throughput RNA inhibition screen to knockdown the genes' expression in both a human lung-derived normal and a tumor cell line. They found that knockdown of ARHGDIA resulted in a two- to four-fold increase in levels of apoptosis in normal cells and the same increase in apoptosis in cancer cells after knockdown of ARHGDIA, COBLL1, and TM4SF1. "We provide evidence that ARHGDIA, COBLL1, and TM4SF1 are negative regulators of apoptosis in cultured tumor cells. These genes, and their related intracellular signaling pathways, may represent potential therapeutic targets in mesothelioma," the authors write.
And finally in BMC Cancer this week, a research team in Australia presents an analysis of the MAP2K4 tumor supressor gene in ovarian cancer. The researchers screened for MAP2K4 mutations in 149 primary ovarian tumors, and found that the frequency of MAP2K4 homozygous inactivation was 5.6 percent overall and 9.8 percent in high-grade serous cases of ovarian cancer. Hemizygous deletion of MAP2K4 was observed in 38 percent of the sameples, the team adds. "MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort," the authors write.