Procyanidin C1 inhibits tumor growth and metastasis in colon cancer via modulating miR-501-3p/HIGD1A axis

Lv, Jun-lin; Tan, Yu-jun; Ren, Yu-shan; Ma, Ru; Wang, Xiao; Wang, Shu-yan; Liu, Wan-qing; Zheng, Qiu-sheng; Yao, Jing-chun; Tian, Jun; Li, Jie

doi:10.1016/j.jare.2023.07.007

Cited by 1 publication

(3 citation statements)

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“…Using PCC1 in a subcutaneous tumour mouse model of gastric cancer showed marked inhibition of tumour growth and a significant decrease in matCAF. This aligns with previous research showing PCC1's role in slowing cellular senescence 27 and impeding colorectal cancer progression 67 …”

Section: Discussionsupporting

confidence: 92%

“…This aligns with previous research showing PCC1's role in slowing cellular senescence 27 and impeding colorectal cancer progression. 67 While some studies highlight the potential for CAF targeting to inadvertently accelerate cancer progression, 68,69 this underscores the diverse roles of various CAF subgroups within the TME. Our focus on matCAF, particularly its link with poorer prognoses in cancer patients due to its oncogenic properties, offers a nuanced perspective.…”

Section: Discussionmentioning

confidence: 99%

“…This aligns with previous research showing PCC1's role in slowing cellular senescence 27 and impeding colorectal cancer progression. 67 …”

Section: Discussionmentioning

confidence: 99%

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The molecular classification of cancer‐associated fibroblasts on a pan‐cancer single‐cell transcriptional atlas

Chen,

Chan,

Xie

et al. 2023

Clinical & Translational Med

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BackgroundCancer‐associated fibroblasts (CAFs), integral to the tumour microenvironment, are pivotal in cancer progression, exhibiting either pro‐tumourigenic or anti‐tumourigenic functions. Their inherent phenotypic and functional diversity allows for the subdivision of CAFs into various subpopulations. While several classification systems have been suggested for different cancer types, a unified molecular classification of CAFs on a single‐cell pan‐cancer scale has yet to be established.MethodsWe employed a comprehensive single‐cell transcriptomic atlas encompassing 12 solid tumour types. Our objective was to establish a novel molecular classification and to elucidate the evolutionary trajectories of CAFs. We investigated the functional profiles of each CAF subtype using Single‐Cell Regulatory Network Inference and Clustering and single‐cell gene set enrichment analysis. The clinical relevance of these subtypes was assessed through survival curve analysis. Concurrently, we employed multiplex immunofluorescence staining on tumour tissues to determine the dynamic changes of CAF subtypes across different tumour stages. Additionally, we identified the small molecule procyanidin C1 (PCC1) as a target for matrix‐producing CAF (matCAF) using molecular docking techniques and further validated these findings through in vitro and in vivo experiments.ResultsIn our investigation of solid tumours, we identified four molecular clusters of CAFs: progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF) and matCAF, each characterised by distinct molecular traits. This classification was consistently applicable across all nine studied solid tumour types. These CAF subtypes displayed unique evolutionary pathways, functional roles and clinical relevance in various solid tumours. Notably, the matCAF subtype was associated with poorer prognoses in several cancer types. The targeting of matCAF using the identified small molecule, PCC1, demonstrated promising antitumour activity.ConclusionsCollectively, the various subtypes of CAFs, particularly matCAF, are crucial in the initiation and progression of cancer. Focusing therapeutic strategies on targeting matCAF in solid tumours holds significant potential for cancer treatment.

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Section: Discussionsupporting

confidence: 92%