p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts

Kimura, Eiji; Hayashi, Yoshito; Nakagawa, Kentaro; Saiki, Hirotsugu; Kato, Minoru; Uema, Ryotaro; Inoue, Takanori; Yoshihara, Takeo; Sakatani, Akihiko; Fukuda, Hiromu; Tajiri, Ayaka; Adachi, Yujiro; Murai, Kazuhiro; Yoshii, Shunsuke; Tsujii, Yoshiki; Shinzaki, Shinichiro; Iijima, Hideki; Takehara, Tetsuo

doi:https://doi.org/10.1111/cas.70026

p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts

Kimura, Eiji; Hayashi, Yoshito; Nakagawa, Kentaro et al.

Cancer Science, 2025

Number of Access:305（2025-06-26 14:51 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/101397

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
CancerSci	pdf	None	8.67 MB	6	2025.06.03

Creative Commons : Attribution - NonCommercial

Item Information

Output File Export EndNote Basic Export Mendeley

Title	p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts
Creator	CreatorName Kimura, Eiji
	NRID 1000080647123 1000080647123 researchmap permalink y-h y-h Scopus Author ID 35219993200 35219993200 CreatorName Hayashi, Yoshito
	CreatorName Nakagawa, Kentaro
	CreatorName Saiki, Hirotsugu
	CreatorName Kato, Minoru
	NRID 1000030939161 1000030939161 researchmap permalink ryotarouema ryotarouema CreatorName Uema, Ryotaro
	CreatorName Inoue, Takanori
	NRID 1000020814601 1000020814601 researchmap permalink ty_gh ty_gh CreatorName Yoshihara, Takeo
	CreatorName Sakatani, Akihiko
	CreatorName Fukuda, Hiromu
	CreatorName Tajiri, Ayaka
	CreatorName Adachi, Yujiro
	NRID 1000050867314 1000050867314 ORCID 0000-0001-8634-2922 0000-0001-8634-2922 researchmap permalink murai_kazuhiro murai_kazuhiro Scopus Author ID 57202460806 57202460806 CreatorName Murai, Kazuhiro
	NRID 1000090771882 1000090771882 CreatorName Yoshii, Shunsuke
	NRID 1000080795170 1000080795170 researchmap permalink yhcks yhcks Scopus Author ID 57192176408 57192176408 CreatorName Tsujii, Yoshiki
	NRID 1000060546860 1000060546860 CreatorName Shinzaki, Shinichiro
	NRID 1000090444520 1000090444520 researchmap permalink _0719 _0719 CreatorName Iijima, Hideki
	NRID 1000070335355 1000070335355 CreatorName Takehara, Tetsuo
Subject	colon cancer
	fibroblasts
	Meflin
	p53
	tumor microenvironment
Description	Kimura E., Hayashi Y., Nakagawa K., et al. p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts. Cancer Science (2025); https://doi.org/10.1111/cas.70026.
Abstract	Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment, play an important role in tumor progression. Colon cancer cells deficient in p53 activate fibroblasts and enhance fibroblast-mediated tumor growth. Meflin is a CAF marker capable of inhibiting tumor growth. In this study, we investigated the role of Meflin in fibroblasts using human cell lines (colon cancer HCT116 and fibroblasts CCD-18Co) and clinical specimens. TP53-suppressed HCT116 (HCT116ˢʰ ᵖ⁵³) cells cocultured with CCD-18Co cells showed significantly faster proliferation than HCT116ˢʰ ᶜᵒⁿᵗʳᵒˡ cells. In xenograft experiments, the volume of tumors induced by coinoculation with HCT116ˢʰ ᵖ⁵³ and CCD-18Co cells was significantly larger than that induced by HCT116ˢʰ ᶜᵒⁿᵗʳᵒˡ cells co-inoculated with CCD-18Co cells. HCT116sh p53 cells increased the levels of CAF-like phenotypic markers in CCD-18Co cells. Moreover, Meflin expression was significantly reduced in CCD-18Co cells cocultured with HCT116ˢʰ ᵖ⁵³ cells compared to that in CCD-18Co cells cocultured with HCT116ˢʰ ᶜᵒⁿᵗʳᵒˡ cells. si-RNA-mediated inhibition of Meflin activated CCD-18Co cells into tumor-promoting CAF-like cells, which significantly promoted xenograft tumor growth. Overexpression of Meflin in CCD-18Co cells using lentivirus suppressed fibroblast-mediated growth of HCT116ˢʰ ᵖ⁵³ tumor xenografts. The expression of Meflin in CCD-18Co cells was suppressed by TGF-β and enhanced by vitamin D. These results indicate that colon cancer cells deficient in p53 suppress Meflin expression in fibroblasts, which affects tumor growth by altering the properties of tumor growth-promoting CAFs. Our results suggest that targeting Meflin in fibroblasts may be a novel therapeutic strategy for colorectal cancer.
Publisher	John Wiley and Sons Inc
Source Title	Cancer Science
Date of Issued	2025-04-16
Language	English
Handle URL	https://hdl.handle.net/11094/101397
PISSN	13479032
eISSN	13497006
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/cas.70026
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 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	Cancer Science. 2025
DC.title	p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts
DC.creator	Kimura, Eiji
	Hayashi, Yoshito
	Nakagawa, Kentaro
	Saiki, Hirotsugu
	Kato, Minoru
	Uema, Ryotaro
	Inoue, Takanori
	Yoshihara, Takeo
	Sakatani, Akihiko
	Fukuda, Hiromu
	Tajiri, Ayaka
	Adachi, Yujiro
	Murai, Kazuhiro
	Yoshii, Shunsuke
	Tsujii, Yoshiki
	Shinzaki, Shinichiro
	Iijima, Hideki
	Takehara, Tetsuo
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-04-16
DC.identifier	https://doi.org/10.1111/cas.70026
DC.subject	colon cancer
	fibroblasts
	Meflin
	p53
	tumor microenvironment
DC.description	Kimura E., Hayashi Y., Nakagawa K., et al. p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts. Cancer Science (2025); https://doi.org/10.1111/cas.70026.
DCTERMS.abstract	Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment, play an important role in tumor progression. Colon cancer cells deficient in p53 activate fibroblasts and enhance fibroblast-mediated tumor growth. Meflin is a CAF marker capable of inhibiting tumor growth. In this study, we investigated the role of Meflin in fibroblasts using human cell lines (colon cancer HCT116 and fibroblasts CCD-18Co) and clinical specimens. TP53-suppressed HCT116 (HCT116ˢʰ ᵖ⁵³) cells cocultured with CCD-18Co cells showed significantly faster proliferation than HCT116ˢʰ ᶜᵒⁿᵗʳᵒˡ cells. In xenograft experiments, the volume of tumors induced by coinoculation with HCT116ˢʰ ᵖ⁵³ and CCD-18Co cells was significantly larger than that induced by HCT116ˢʰ ᶜᵒⁿᵗʳᵒˡ cells co-inoculated with CCD-18Co cells. HCT116sh p53 cells increased the levels of CAF-like phenotypic markers in CCD-18Co cells. Moreover, Meflin expression was significantly reduced in CCD-18Co cells cocultured with HCT116ˢʰ ᵖ⁵³ cells compared to that in CCD-18Co cells cocultured with HCT116ˢʰ ᶜᵒⁿᵗʳᵒˡ cells. si-RNA-mediated inhibition of Meflin activated CCD-18Co cells into tumor-promoting CAF-like cells, which significantly promoted xenograft tumor growth. Overexpression of Meflin in CCD-18Co cells using lentivirus suppressed fibroblast-mediated growth of HCT116ˢʰ ᵖ⁵³ tumor xenografts. The expression of Meflin in CCD-18Co cells was suppressed by TGF-β and enhanced by vitamin D. These results indicate that colon cancer cells deficient in p53 suppress Meflin expression in fibroblasts, which affects tumor growth by altering the properties of tumor growth-promoting CAFs. Our results suggest that targeting Meflin in fibroblasts may be a novel therapeutic strategy for colorectal cancer.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	101397
citation_title	p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts
citation_author	Kimura, Eiji
	Hayashi, Yoshito
	Nakagawa, Kentaro
	Saiki, Hirotsugu
	Kato, Minoru
	Uema, Ryotaro
	Inoue, Takanori
	Yoshihara, Takeo
	Sakatani, Akihiko
	Fukuda, Hiromu
	Tajiri, Ayaka
	Adachi, Yujiro
	Murai, Kazuhiro
	Yoshii, Shunsuke
	Tsujii, Yoshiki
	Shinzaki, Shinichiro
	Iijima, Hideki
	Takehara, Tetsuo
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2025-04-16
citation_journal_title	Cancer Science
citation_doi	https://doi.org/10.1111/cas.70026
citation_public_url	https://hdl.handle.net/11094/101397

p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts

Link to primary information

Item Information

Show details