7009

TMBIM6

transmembrane BAX inhibitor motif containing 6;TMBIM6;transmembrane BAX inhibitor motif containing 6

bax inhibitor 1|testis enhanced gene transcript|testis-enhanced gene transcript protein|transmembrane BAX inhibitor motif-containing protein 6

12q13.12

protein-coding

The overexpression of BI-1 induces an acidic extracellular pH due to alterations of mitochondrial function, leading to cancer metastasis through anaerobic glucose metabolism. In this study, ion transporters such as sodium hydrogen exchangers (NHE) and monoamine carboxylate transporters (MCTs) were studied in BI-1-overexpressing HT1080 cells (BI-1 cells). The extracellular pH became acidic as culture time of BI-1 cells increased, while intracellular pH stayed relatively stable at pH 7.2. The expression of MCTs increased in BI-1 cells as culture time passed. 5-(N-ethyl-N-isopropyl) amiloride or dimethylamiloride, NHE inhibitor, abrogated the elevated MCT expression, indicating that MCT followed NHE activation. An MCT inhibitor, lonidamine, regulated the acidification of extracellular pH, also inhibiting both increased cancer cell migration and infiltration and MMP2/9 activity. The inhibition of either NHE or MCT affected the intracellular pH, leading to a severely acidic intracellular pH and cell death. In BI-1 cells, the activation of ion transporters such as NHE or MCT may offer a survival strategy against metabolism-associated acidic stresses. These findings suggest that BI-1 can lead cancer invasion and metastasis by inducing extracellular environment acidic.

Bax inhibitor-1 (BI1) family contains six known genes in human. Some members of BI1 family have been proved to play important roles in cell death. Here we discuss the similarities and differences among the members of BI1 family by comparative genomics and proteomics, and report here the discovery of a novel member, tmbim1b, in Bos taurus. BI1 family is evolutionarily conserved as integral membrane proteins containing multiple membrane-spanning segments and predominantly localized to intracellular membranes, similar to Bcl-2 family proteins. They share multiple motifs and transcriptional factors within the promoter and the coding regions. They may represent regulators of cell death pathways, which are concluded from structure conservation of BI1 family.