TCAF1 puts a chill on prostate cancer

The partner of a cold-sensing ion channel prevents prostate cancer cells from migrating, Gkika et al. reveal.

The ion channel TRPM8 detects low temperatures, but it occurs in parts of the body that aren’t exposed to the cold, such as the prostate and bladder, suggesting that it has other roles. The protein is overexpressed in prostate tumors and other cancers, and the researchers previously determined that it curbs migration of prostate cancer cells.

Gkika et al. looked for proteins that interact with TRPM8. Two of its partners were previously uncharacterized proteins that the authors named TCAF1 and TCAF2. The researchers found that TCAF1 and TCAF2 help TRPM8 move into the plasma membrane. However, the proteins have opposite effects on TRPM8’s activity. TCAF1 stimulates the channel, whereas TCAF2 shuts it down. The difference appears to lie in TCAF1’s tail, which, unlike TCAF2’s, sports a domain that is homologous to PI3K.

TCAF2 levels were the same in normal and cancerous cells. But like TRPM8, TCAF1 was overexpressed in prostate cancers that hadn’t spread, whereas in metastatic prostate cancer cells the levels of TRPM8 and TCAF1 plunged, likely as a side effect of the treatment the patients had received to suppress androgen production.

The researchers found that TCAF1 slowed migration of prostate cancer cells in vitro but that TCAF2 stimulated cell motility. The work suggests that TCAF proteins regulate TRPM8 and possibly other TRP channels, functioning like the accessory subunits that control the activity and location of voltage-gated channels.