Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth

Kato, Shinya; Miyoshi, Norikatsu; Fujino, Shiki; Horie, Masafumi; Yachida, Shinichi; Takeda, Mitsunobu; Sekido, Yuki; Hata, Tsuyoshi; Hamabe, Atsushi; Ogino, Takayuki; Uemura, Mamoru; Yamamoto, Hirofumi; Yasui, Masayoshi; Ohue, Masayuki; Doki, Yuichiro; Eguchi, Hidetoshi

doi:https://doi.org/10.1245/s10434-025-17765-0

Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth

Kato, Shinya; Miyoshi, Norikatsu; Fujino, Shiki et al.

Annals of Surgical Oncology, 2025

Number of Access:39（2025-10-21 10:04 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102742

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Title	Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth
Creator	NRID 1000050912010 1000050912010 Scopus Author ID 57772973700 57772973700 CreatorName Kato, Shinya
	NRID 1000020528624 1000020528624 ORCID 0000-0003-1113-8884 0000-0003-1113-8884 researchmap permalink nor nor Scopus Author ID 9242781300 9242781300 CreatorName Miyoshi, Norikatsu
	NRID 1000010768956 1000010768956 ORCID 0000-0003-0302-5337 0000-0003-0302-5337 researchmap permalink oicc_miyshilab oicc_miyshilab Scopus Author ID 56362736200 56362736200 CreatorName Fujino, Shiki
	CreatorName Horie, Masafumi
	NRID 1000020359920 1000020359920 ORCID 0000-0001-5507-4566 0000-0001-5507-4566 researchmap permalink read0210591 read0210591 Scopus Author ID 57226203270 57226203270 CreatorName Yachida, Shinichi
	NRID 1000090768962 1000090768962 researchmap permalink takeda27832 takeda27832 CreatorName Takeda, Mitsunobu
	NRID 1000000781709 1000000781709 ORCID 0000-0003-4281-0047 0000-0003-4281-0047 researchmap permalink 00781709 00781709 Scopus Author ID 57193691322 57193691322 CreatorName Sekido, Yuki
	NRID 1000080749747 1000080749747 researchmap permalink tsuyoshi_hata tsuyoshi_hata Scopus Author ID 57189996374 57189996374 CreatorName Hata, Tsuyoshi
	NRID 1000060621034 1000060621034 ORCID 0000-0001-5535-3514 0000-0001-5535-3514 researchmap permalink hamabe_atsushi hamabe_atsushi Scopus Author ID 26435224200 26435224200 CreatorName Hamabe, Atsushi
	NRID 1000050597458 1000050597458 ORCID 0000-0001-5435-4144 0000-0001-5435-4144 researchmap permalink togino04 togino04 Scopus Author ID 57200254430 57200254430 CreatorName Ogino, Takayuki
	NRID 1000010528483 1000010528483 ORCID 0000-0001-6285-5619 0000-0001-6285-5619 researchmap permalink mamoruuemura mamoruuemura Scopus Author ID 36796497400 36796497400 CreatorName Uemura, Mamoru
	NRID 1000030322184 1000030322184 researchmap permalink kobunyam kobunyam Scopus Author ID 12805320700 12805320700 CreatorName Yamamoto, Hirofumi
	CreatorName Yasui, Masayoshi
	NRID 1000040294095 1000040294095 CreatorName Ohue, Masayuki
	NRID 1000020291445 1000020291445 researchmap permalink ydoki3251 ydoki3251 Scopus Author ID 7006390687 7006390687 CreatorName Doki, Yuichiro
	NRID 1000090542118 1000090542118 researchmap permalink abcdabcdabcd abcdabcdabcd Scopus Author ID 7101627772 7101627772 ORCID 0000-0002-2318-1129 0000-0002-2318-1129 CreatorName Eguchi, Hidetoshi
Subject	ACRV1
	BMP7–ACRV1 axis
	Cancer-associated fibroblast
	Colorectal cancer
	Organoid culture
	Tumor growth inhibition
	Two-dimensional organoid
Description	The version of record of this article, first published in Annals of Surgical Oncology (2025), is available online at Publisher’s website: https://doi.org/10.1245/s10434-025-17765-0.
Abstract	Background: Colorectal cancer (CRC) is the third most common malignancy worldwide and a leading cause of cancer-related mortality. Stromal signatures in CRC are correlated with poor prognosis and resistance to chemotherapy, affecting tumor progression and relapse. Although single-cell analyses have identified subpopulations of cancer-associated fibroblasts (CAFs), effective molecular targeted therapies against CAFs are lacking. Materials and Methods: We employed organoid culture methods, focusing on two-dimensional organoids (2DOs) to mimic CRC histology. Using single-cell analysis, we investigated cancer-fibroblast crosstalk, with emphasis on activin receptor type I (ACVR1) in fibroblasts and bone morphogenetic protein 7 (BMP7) in cancer cells as potential therapeutic targets. The correlation between high ACVR1 and BMP7 expression levels and the prognosis of patients with stage II cancer was evaluated. Results: The 2DO mouse xenograft model replicated the characteristics of the fibroblast subpopulations present in human CRC tumors. Single-cell RNA sequencing identified fibroblast clusters, with the BMP7–ACVR1 axis emerging as a potential therapeutic target. High BMP7 and ACVR1 expression was significantly correlated with poor disease-free survival and overall survival in stage II CRC. Administration of an ACVR1 inhibitor during the coculture of 2DOs and mouse stromal cells inhibited tumor growth. Conclusions: ACVR1 is a promising therapeutic target that inhibits CAF proliferation. High BMP7 and ACVR1 expression is a significant prognostic factor in stage II CRC.
Publisher	Springer Science and Business Media Deutschland GmbH
Source Title	Annals of Surgical Oncology
Date of Issued	2025-07-31
Language	English
Handle URL	https://hdl.handle.net/11094/102742
PISSN	10689265
eISSN	15344681
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1245/s10434-025-17765-0
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Annals of Surgical Oncology. 2025
DC.title	Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth
DC.creator	Kato, Shinya
	Miyoshi, Norikatsu
	Fujino, Shiki
	Horie, Masafumi
	Yachida, Shinichi
	Takeda, Mitsunobu
	Sekido, Yuki
	Hata, Tsuyoshi
	Hamabe, Atsushi
	Ogino, Takayuki
	Uemura, Mamoru
	Yamamoto, Hirofumi
	Yasui, Masayoshi
	Ohue, Masayuki
	Doki, Yuichiro
	Eguchi, Hidetoshi
DC.publisher	Springer Science and Business Media Deutschland GmbH
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-07-31
DC.identifier	https://doi.org/10.1245/s10434-025-17765-0
DC.subject	ACRV1
	BMP7–ACRV1 axis
	Cancer-associated fibroblast
	Colorectal cancer
	Organoid culture
	Tumor growth inhibition
	Two-dimensional organoid
DC.description	The version of record of this article, first published in Annals of Surgical Oncology (2025), is available online at Publisher’s website: https://doi.org/10.1245/s10434-025-17765-0.
DCTERMS.abstract	Background: Colorectal cancer (CRC) is the third most common malignancy worldwide and a leading cause of cancer-related mortality. Stromal signatures in CRC are correlated with poor prognosis and resistance to chemotherapy, affecting tumor progression and relapse. Although single-cell analyses have identified subpopulations of cancer-associated fibroblasts (CAFs), effective molecular targeted therapies against CAFs are lacking. Materials and Methods: We employed organoid culture methods, focusing on two-dimensional organoids (2DOs) to mimic CRC histology. Using single-cell analysis, we investigated cancer-fibroblast crosstalk, with emphasis on activin receptor type I (ACVR1) in fibroblasts and bone morphogenetic protein 7 (BMP7) in cancer cells as potential therapeutic targets. The correlation between high ACVR1 and BMP7 expression levels and the prognosis of patients with stage II cancer was evaluated. Results: The 2DO mouse xenograft model replicated the characteristics of the fibroblast subpopulations present in human CRC tumors. Single-cell RNA sequencing identified fibroblast clusters, with the BMP7–ACVR1 axis emerging as a potential therapeutic target. High BMP7 and ACVR1 expression was significantly correlated with poor disease-free survival and overall survival in stage II CRC. Administration of an ACVR1 inhibitor during the coculture of 2DOs and mouse stromal cells inhibited tumor growth. Conclusions: ACVR1 is a promising therapeutic target that inhibits CAF proliferation. High BMP7 and ACVR1 expression is a significant prognostic factor in stage II CRC.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	102742
citation_title	Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth
citation_author	Kato, Shinya
	Miyoshi, Norikatsu
	Fujino, Shiki
	Horie, Masafumi
	Yachida, Shinichi
	Takeda, Mitsunobu
	Sekido, Yuki
	Hata, Tsuyoshi
	Hamabe, Atsushi
	Ogino, Takayuki
	Uemura, Mamoru
	Yamamoto, Hirofumi
	Yasui, Masayoshi
	Ohue, Masayuki
	Doki, Yuichiro
	Eguchi, Hidetoshi
citation_publisher	Springer Science and Business Media Deutschland GmbH
citation_language	English
citation_date	2025-07-31
citation_journal_title	Annals of Surgical Oncology
citation_doi	https://doi.org/10.1245/s10434-025-17765-0
citation_public_url	https://hdl.handle.net/11094/102742

Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth

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