Inhibiting IGF1R-mediated Survival Signaling in Head and Neck Cancer with the Peptidomimetic SSTN_IGF1R.

ABSTRACT: Previous studies have shown that the type I IGFR (IGF1R) suppresses apoptosis when it is autoactivated by coupling its extracellular domain to a matrix adhesion receptor complex consisting of syndecan-1 (Sdc1) and αvβ3 or αvβ5 integrin. We now report that head and neck squamous cell carcinoma (HNSCC) relies on this receptor complex. Disruption of the complex in HNSCC cells in vitro with a peptide mimetic of the organizer site in Sdc1 (called SSTN_IGF1R) inactivates IGF1R, even in the presence of IGF1, and relieves the suppression of apoptosis signal-regulating kinase-1 (ASK1), dramatically reducing tumor cell survival. Normal epithelial cells do not assemble this receptor complex, require IGF1 to activate the IGF1R, and are refractory to SSTN_IGF1R. In vivo

SUBMITTER: Stueven NA 

PROVIDER: S-EPMC10035507 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature