ArticleOncogene2013
p16(INK4A) represses the paracrine tumor-promoting effects of breast stromal fibroblasts.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 91 citations in OpenAlex.
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- Identification and validation of a refined CAF-Associated diagnostic signature in breast cancer.Scientific reports · 2026Article
- Crosstalk between heterogeneous cancer-associated fibroblast subpopulations and the immune system in breast cancer: key players and promising therapeutic targets.Journal of experimental & clinical cancer research : CR · 2025Review
- CAFs exosomal circFOXO1 promotes TNBC autophagy and radioresistance via miR-27a-3p/BNIP3 axis.Scientific reports · 2025Article
- Expression and clinical significance of AUF1 and HIF-1α in papillary thyroid carcinoma.World journal of surgical oncology · 2025Article
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- Deciphering the stromal molecular landscape: the correlation between p16 and α-SMA in epithelial ovarian cancer.Journal of cancer research and clinical oncology · 2025Article
- E2F1 activates breast stromal fibroblasts and promotes their paracrine pro-carcinogenic effects.Scientific reports · 2025Article
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- Characterization of cancer-associated fibroblasts (CAFs) and development of a CAF-based risk model for triple-negative breast cancer.Cancer cell international · 2023Article
- Activated breast stromal fibroblasts exhibit myoepithelial and mammary stem cells features.Translational oncology · 2023Article
- Adverse Crosstalk between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer.Cells · 2023Article
- Tissue Extract from Brittle Star Undergoing Arm Regeneration Promotes Wound Healing in Rat.Marine drugs · 2023Article
- Review
- High AUF1 level in stromal fibroblasts promotes carcinogenesis and chemoresistance and predicts unfavorable prognosis among locally advanced breast cancer patients.Breast cancer research : BCR · 2022Article
- Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer.Oncoimmunology · 2022Article
- Breast Cancer CAFs: Spectrum of Phenotypes and Promising Targeting Avenues.International journal of molecular sciences · 2021Review
- A novel lncRNA derived from an ultraconserved region: lnc-RNA biology · 2021Article
- [Comparison of two methods for preparing knee osteochondral injury models in mice].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2021Article
- AUF1 Promotes Proliferation and Invasion of Thyroid CancerFrontiers in oncology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs), the most abundant and probably the most active cellular component of breast cancer-associated stroma, promote carcinogenesis through paracrine effects; however, the molecular basis remains elusive. We have shown here that p16(INK4A) expression is reduced in 83% CAFs as compared with their normal adjacent counterparts cancer-free tissues isolated from the same patients. This decrease is mainly due to AUF1-dependent higher turnover of the CDKN2A mRNA in CAFs. Importantly, p16(INK4A) downregulation using specific siRNA activated breast fibroblasts and increased the expression/secretion levels of stromal cell-derived factor 1 (SDF-1) and matrix metalloproteinase (MMP)-2. Consequently, media conditioned with these cells stimulated the proliferation of epithelial cells. Furthermore, the migration/invasion of breast cancer cells was also enhanced in an SDF-1-dependent manner. This effect was mediated through inducing an epithelial-mesenchymal transition state. By contrast, increase in p16(INK4A) level through ectopic expression or AUF1 downregulation, reduced the secreted levels of SDF-1 and MMP-2 and suppressed the pro-carcinogenic effects of CAFs. In addition, p16(INK4A)-defective fibroblasts accelerated breast tumor xenograft formation and growth rate in mice. Importantly, tumors formed in the presence of p16(INK4A)-defective fibroblasts exhibited higher levels of active Akt, Cox-2, MMP-2 and MMP-9, showing their greater aggressiveness as compared with xenografts formed in the presence of p16(INK4A)-proficient fibroblasts. These results provide the first indication that p16(INK4A) downregulation in breast stromal fibroblasts is an important step toward their activation.
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