Overexpression of Caveolin-1 in Cancer-Associated Fibroblasts Predicts Good Outcome in Breast Cancer

Wang, Shan-wei; Xu, Ke; Ruan, Shu-qin; Zhao, Lili; Chen, Lirong

doi:10.1159/000345464

Cited by 24 publications

(13 citation statements)

References 18 publications

(21 reference statements)

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“…Lisanti et al called this concept the “reverse Warburg effect” [ 87 ], as CAFs contribute as the source of energy in cancer cells. Overexpression of caveolin-1 in breast cancer predicts a good outcome [ 88 ]. In recent studies, this form of energy metabolism in cancer tissues has been a target of anticancer treatments [ 89 ].…”

Section: The Role Of Cafsmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

Shiga

Hara

Nagasaki

et al. 2015

Cancers

659

538

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Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy.

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Section: The Role Of Cafsmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

Shiga

Hara

Nagasaki

et al. 2015

Cancers

659

538

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“…Clearly small tumors enriched for CD146 -CAFs require aggressive treatments. caveolin 1, α-smooth muscle actin, fibroblast-specific protein 1, α-and β-platelet-derived growth factor, vimentin, and others (7,8).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast subtypes define a metastatic matrisome in breast cancer

Brechbuhl¹,

Barrett²,

Kopin³

et al. 2020

JCI Insight

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“…Both, CAV1 and IGFBP6 were selected for their association to the mesenchymal phenotype of Hh-responsive stroma. Downregulation of CAV1 has been linked with cancer-associated fibroblasts (19) and its overexpression in tumor adjacent stroma is a good predictor of improved outcome in breast cancer(20). IGFBP-6 is a target of Hedgehog signaling in the tumor adjacent stroma (21, 22).…”

Section: Resultsmentioning

confidence: 99%

Hedgehog-mesenchyme gene signature identifies bi-modal prognosis in luminal and basal breast cancer sub-types

Torres-García

Domenech

2017

Mol. BioSyst.

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Hedgehog signaling (Hh) has been shown to be hyper-activated in several cancers. However, active Hh signaling can promote or inhibit tumor growth, thus identification of markers beyond main canonical Hh target genes are needed to improve patient selection and clinical outcome in response to Hh inhibitors. Cancer-associated fibroblast (CAFs) have been linked with tumor progression and beneficial response to Hh inhibitors. Thus, we hypothesized that genes associated with Hh-activated CAFs can be used for stratification of tumors that will benefit from Hh inhibitors. In this work, we evaluated a 15-gene fingerprint that combines Hh and mesenchymal genes associated to CAFs phenotype to profile breast cancer sub-types based on gene expression patterns among clustered groups. About 3,800 cancer samples were evaluated using random forest models and linear discriminant analysis to sort breast cancer by subtypes and therapeutic approach. Results showed that the Hh-mesenchyme gene fingerprint has a highly sensitive and differential expression pattern among basal and luminal A sub-groups. Basal samples with high levels of Hh target genes had better prognosis than Luminal A samples. Luminal A samples with tendency towards Hh signaling suppression had higher overall and disease-free survival rates particularly if deprived of hormone therapy. Hh transcriptional repressor GLI3 and signaling activator SMO were the top 2 genes to discriminate among samples with active Hh signaling in human breast cancer subtypes and Hh-inhibitor resistant tumors. Caveolin-1 (CAV1), a gene associated to low expression in CAFs, shows strong correlation with active Hh signaling and discrimination among survival curves in Luminal A patients with active or inactive Hh signaling. Our data suggests that CAV1 is an important gene for monitoring Hh inhibition in tumors and supports further stratification by hormone therapy status prior to use of Hh inhibitors.

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Overexpression of Caveolin-1 in Cancer-Associated Fibroblasts Predicts Good Outcome in Breast Cancer

Cited by 24 publications

References 18 publications

Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

Fibroblast subtypes define a metastatic matrisome in breast cancer

Hedgehog-mesenchyme gene signature identifies bi-modal prognosis in luminal and basal breast cancer sub-types

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