Abstract 6028: The impact of CAF-derived ANKRD1 on the lung cancer tumor microenvironment

Abstract Background: Cancer-associated fibroblasts (CAFs) constitute a major component of the tumor microenvironment (TME) and are key drivers of cancer progression, therapeutic resistance, and malignancy. To improve treatment outcomes in lung cancer, it is essential to identify stromal factors that contribute to tumor aggressiveness. Methods: RNA sequencing was performed to compare gene expression profiles between normal fibroblasts (NFs) and CAFs. Clinical databases were analyzed to determine the prognostic significance of ANKRD1 expression in lung cancer. We investigated whether cancer-derived stimuli activate ANKRD1 in NFs by exposing them to cancer cell-derived growth factors. NFs with overexpressed ANKRD1 were established and used to evaluate the effects of ANKRD1 on migration ability and treatment resistance through migration assays and colony formation assays. The effects on angiogenesis were assessed by measuring VEGF secretion and performing HUVEC (Human Umbilical Vein Endothelial Cells) tube formation assays. Results: ANKRD1 was significantly overexpressed in CAFs compared to NFs and was associated with poor prognosis, particularly in lung adenocarcinoma. TGF-β stimulation induced ANKRD1 expression in NFs. ANKRD1-overexpressing NFs exhibited enhanced migratory ability and increased therapeutic resistance. Conditioned medium from ANKRD1-overexpressing NFs promoted VEGF secretion by cancer cells and enhanced angiogenic activity in HUVECs, suggesting that ANKRD1 activation contributes to angiogenesis both indirectly and directly. Conclusions: ANKRD1 activation in fibroblasts within the lung cancer TME promotes tumor progression, angiogenesis, and treatment resistance through fibroblast-cancer cell crosstalk. These findings highlight ANKRD1 as a promising therapeutic target for modulating the TME and improving lung cancer outcomes. Citation Format: Kazuhiro Okada, Ken Suzawa, Shunsuke Mori, Kenta Manabe, Ryunosuke Fujii, Kousei Ishimura, Ryota Fujiwara, Kazuya Hisamatsu, Ryo Yoshichika, Atsushi Matsuoka, Yuma Fukumoto, Hidejiro Torigoe, Kazuhiko Shien, Shinichi Toyooka. The impact of CAF-derived ANKRD1 on the lung cancer tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6028.