Ligand-dependent transcriptional heterogeneity in cell cycle gene expression delays G1/S entry.

Authors

Ririn Rahmala Febri, Ayaka Nagasato-Ichikawa, Keita Iida, Shuhei Kimura, Akira Imamoto, Mariko Okada

Published in

FEBS letters. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

ErbB ligands activate distinct receptor dimers that regulate cell proliferation, but how they influence cell-cycle commitment remains unclear. Here, we show that EGF and HRG induce different modes of G1/S progression in ErbB2-amplified BT474 breast cancer cells. Unexpectedly, HRG, despite activating the more potent ErbB2-ErbB3 heterodimer, failed to accelerate G1/S progression; instead, EGF promoted earlier passage through the restriction point and faster S-phase entry. Mechanistically, EGF drove rapid and coordinated cell-cycle progression through ERK-FOS signaling, whereas HRG induced sustained MYC activity, elevated transcriptional heterogeneity, and caused extensive rewiring of cell-cycle regulatory networks. Together, these findings reveal that ligand-specific ErbB signaling controls not only the timing of cell-cycle entry but also the transcriptional architecture that governs proliferative fate decisions.

PMID:
42629963
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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