Activity over Abundance: ADAMTSL4 Unlocks Latent TGFβ1 in Cancer Cachexia.

ADAMTSL4 secreted by tumors activates latent TGFβ1, driving tissue wasting in cancer cachexia, highlighting a new therapeutic target.

• Why it matters: Cancer cachexia involves complex interorgan communication that leads to severe tissue loss, yet the molecular mechanisms controlling this process are not fully understood, limiting treatment options.
• What they did: Machado and colleagues identified that tumor-secreted ADAMTSL4 promotes cachexia by locally activating latent TGFβ1, revealing a post-secretory control point of ligand activation.
• The result: This discovery suggests targeting ADAMTSL4 or its pathway could prevent or mitigate tissue wasting in cancer cachexia, opening new avenues for therapeutic intervention.