Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.

Tumor-secreted ADAMTSL4 activates latent TGFβ1, driving multiorgan wasting and fibrosis in cancer cachexia, with levels correlating to disease severity.

• Why it matters: Cancer cachexia causes severe weight loss and morbidity, yet effective treatments are lacking. Understanding its molecular drivers could enable targeted therapies to improve patient outcomes.
• What they did: The study identified ADAMTSL4 as a tumor-derived glycoprotein linked to cachexia in models and patients, demonstrating that manipulating its expression influences muscle and fat wasting through TGFβ1 activation.
• The result: Blocking ADAMTSL4 reduced muscle atrophy and fibrosis, highlighting it as a promising therapeutic target that may offer a more selective approach than systemic TGFβ pathway inhibition.