Juliano Machado, Postdoctoral Researcher at Helmholtz Munich, shared on X:
“Excited to share our new study, now published in Cancer Discovery!
We identify tumor-secreted ADAMTSL4 as a previously unknown driver of cancer cachexia, promoting skeletal muscle and adipose tissue wasting.
Circulating ADAMTSL4 was elevated across preclinical models of cachexia and in patients with colorectal and lung cancer, where higher levels were associated with greater weight loss and cachexia severity.
Tumor-specific gain- and loss-of-function experiments showed that ADAMTSL4 is sufficient to induce systemic wasting and that reducing tumor-derived ADAMTSL4 preserves skeletal muscle and adipose tissue.
Mechanistically, we uncovered a previously unrecognized interaction between ADAMTSL4 and latent TGF-β1.
ADAMTSL4 promotes local TGF-β activation at the muscle cell surface, triggering downstream catabolic and fibrotic programs.
Rather than targeting TGF-β systemically, our findings suggest that interfering with tumor-derived ADAMTSL4 could provide a more selective strategy to counteract cancer-associated tissue wasting.
Read our study in Cancer Discovery.
Title: Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia
Authors: Juliano Machado, Vignesh Karthikaisamy, Hermine Mohr, Doris Kaltenecker, Pia Benedikt, Pauline Morigny, Amit Mhamane, Julia Geppert, Amy Rose Fumo, Kerstin Haase, Estefania Simoes, Joanna D.C.C. Lima, Anastasia Georgiadi, Achim Krüger, José Pinhata Otoch, Marc E. Martignoni, Vickie E. Baracos, Mariam Jamal-Hanjani, Marilia C.L. Seelaender, Olga Prokopchuk, Julia Szendrödi, Maria Rohm, Stephan Herzig
Extremely grateful to Mauricio, Berriel Diaz, Stephan Schindler, Herzig, Helmholtz Munich and all our co-authors and collaborators who made this work possible.
Read the Helmholtz Munich press release.
Grateful for this milestone – and excited to see what the next chapter will bring.”
You can also read: CancerWorld Explores a New Mechanism Behind Cancer Cachexia
