ATF4 and FGFR4 cooperatively support thyroid cancer progression and CAF-associated tumor-promoting features.

Authors

Jinsong Zhang, Jiehao Cai, Weihong Ruan

Published in

Endocrine. Volume 91. Issue 1. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Aggressive thyroid cancer remains difficult to treat, partly because molecular programs linking malignant behavior to cancer-associated fibroblast (CAF)-related support are incompletely defined. This study investigated whether ATF4 and FGFR4 cooperate in thyroid cancer cells and whether this relationship persists in a CAF-associated context.
Stable ATF4 and/or FGFR4 knockdown was established in 8305 C thyroid cancer cells. Proliferation, migration, invasion, apoptosis, cytokine secretion, transcriptomic changes, and xenograft growth were assessed under basal and CAF-conditioned culture conditions.
Silencing ATF4 or FGFR4 reduced 8305 C cell proliferation, migration, and invasion, with the strongest inhibition after combined knockdown. These effects persisted in CAF-conditioned medium and were accompanied by increased apoptosis, reduced IL-6 and TNF-α secretion, and transcriptomic changes involving cell cycle, stress-response, apoptosis, and inflammatory pathways. In vivo, ATF4 and/or FGFR4 silencing suppressed xenograft growth, increased tumor apoptosis, and reduced CAF-associated marker expression.
ATF4 and FGFR4 are functionally associated in thyroid cancer progression. Their cooperative program may contribute to cancer cell aggressiveness and to the maintenance of a CAF-associated tumor-promoting microenvironment.

PMID:
42603241
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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