A Mouse Model to Investigate the Role of Cancer-associated Fibroblasts in Tumor Growth

Jelínek, David; Zhang, Ellen Ran; Ambrus, Aaron M.; Haley, Erin M.; Guinn, Emily; Vo, Austin; Le, Peter; Kesaf, Ayse Elif; Nguyen, Jennifer; Guo, Lily; Frederick, Destiny; Sun, Zhenjie; Guo, Natalie; Sevier, Parker; Bilotta, Eric M.; Atai, Kaiser; Voisin, Laurent; Coller, Hilary A.

doi:10.3791/61883

Cited by 4 publications

(1 citation statement)

References 49 publications

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“…Tumor adjacent tissue and extracellular matrix are also key to fully understand metastasis. Jelinek et al 5 provide a PDX to study cancer associated fibroblasts' impact on tumor growth, using patient derived dermal fibroblasts to co-inject with human melanoma cell lines. Mayorca-Guiliani et al 6 describe a method to decellularize mice heart and lungs and generate an intact scaffold, which may be used to seed cells, and more importantly, to understand the location/topology and extracellular matrix (ECM) composition of these organs.…”

Section: Editorialmentioning

confidence: 99%

Preclinical Models and Imaging Modalities of the Tumor Microenvironment in Metastasis

Sousa

2023

JoVE

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Section: Editorialmentioning

confidence: 99%

Preclinical Models and Imaging Modalities of the Tumor Microenvironment in Metastasis

Sousa

2023

JoVE

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Opposing USP19 splice variants in TGF-β signaling and TGF-β-induced epithelial–mesenchymal transition of breast cancer cells

Zhang

Dinther

Thorikay

et al. 2023

Cell. Mol. Life Sci.

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Ubiquitin-specific protease (USP)19 is a deubiquitinating enzyme that regulates the stability and function of multiple proteins, thereby controlling various biological responses. The alternative splicing of USP19 results in the expression of two major encoded variants that are localized to the endoplasmic reticulum (ER) (USP19-ER) and cytoplasm (USP19-CY). The importance of alternative splicing for the function of USP19 remains unclear. Here, we demonstrated that USP19-CY promotes TGF-β signaling by directly interacting with TGF-β type I receptor (TβRI) and protecting it from degradation at the plasma membrane. In contrast, USP19-ER binds to and sequesters TβRI in the ER. By decreasing cell surface TβRI levels, USP19-ER inhibits TGF-β/SMAD signaling in a deubiquitination-independent manner. Moreover, USP19-ER inhibits TGF-β-induced epithelial–mesenchymal transition (EMT), whereas USP19-CY enhances EMT, as well as the migration and extravasation of breast cancer cells. Furthermore, USP19-CY expression is correlated with poor prognosis and is higher in breast cancer tissues than in adjacent normal tissues. Notably, the splicing modulator herboxidiene inhibits USP19-CY, increases USP19-ER expression and suppresses breast cancer cell migration. Targeting USP19 splicing or its deubiquitinating activity may have potential therapeutic effects on breast cancer.

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High-precision targeting and destruction of cancer-associated PDGFR-β+ stromal fibroblasts through self-assembling, protein-only nanoparticles

Voltà-Durán,

Alba-Castellón,

Serna

et al. 2023

Acta Biomaterialia

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A Mouse Model to Investigate the Role of Cancer-associated Fibroblasts in Tumor Growth

Cited by 4 publications

References 49 publications

Preclinical Models and Imaging Modalities of the Tumor Microenvironment in Metastasis

Preclinical Models and Imaging Modalities of the Tumor Microenvironment in Metastasis

Opposing USP19 splice variants in TGF-β signaling and TGF-β-induced epithelial–mesenchymal transition of breast cancer cells

High-precision targeting and destruction of cancer-associated PDGFR-β+ stromal fibroblasts through self-assembling, protein-only nanoparticles

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