Methyltransferase-like 17 physically and functionally interacts with estrogen receptors.

Estrogen exerts its physiological and pathological functions through two estrogen receptors (ERs), ERα and ERß, which act as transcription factors. Coregulators, including coactivators and corepressors, have been shown to be crucial for regulation of ER transcriptional activity. Although many coregulators have been identified to regulate activities of ERs, novel coregulators are still needed to be investigated. Here, we show that human methyltransferase-like 17 (METTL17), whose function is unknown, physically interacts with ERα and ERß, and functionally acts as a coactivator for ERs. METTL17 interacts with ER in vitro and in yeast and mammalian cells. Activation function-1 (AF1) and AF2 domains of ERs are responsible for the interaction between METTL17 and ERs. Knockdown of METTL17 reduces transcriptional activities of ERα and ERß in breast cancer cells, whereas METTL17 overexpression increases ERα and ERß transcriptional activities. Inhibition of METTL17 expression decreases mRNA and protein levels of ER target genes, including PR, cathepsin D, and pS2. Moreover, METTL17 knockdown reduces breast cancer cell growth. These results indicate that METTL17 is a novel coactivator of ERs and may play a role in breast tumorigenesis.

FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest.

Four and a half LIM protein 1 (FHL1) has been characterized as a tumor suppressor in various types of tumor. However, the biological function and underlying mechanism of FHL1 in tongue squamous cell carcinoma (TSCC) remain to be elucidated. The present study demonstrated that FHL1 inhibits anchorage­dependent and ­independent growth of TSCC cells in vitro and tumor growth in nude mice, as determined by cell proliferation and soft agar assays. Knockdown of FHL1 with FHL1 small interfering RNA (siRNA) promoted tumor growth in nude mice. Mechanistically, flow cytometric analysis showed that knockdown of FHL1 promoted G1/S cell cycle progression. Furthermore, expression of cell cycle­associated regulators, cyclin D and cyclin E, were detected by western blotting and reverse transcription­quantitative polymerase chain reaction. Cyclin D and cyclin E were markedly elevated at both the protein and mRNA level in the FHL1 siRNA­transfected cells. These results suggested that FHL1 has a tumor suppressive role in TSCC and that FHL1 may be a useful target for TSCC gene therapy.