ArticleCell communication and signaling : CCS2024
Bcl-2 dependent modulation of Hippo pathway in cancer cells.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Research on the Hippo Pathway in Cancer.Cells · 2026Review
- Challenges and advances in drug resistance and tolerance in cancer.Journal of experimental & clinical cancer research : CR · 2026Review
- AFP confers the resistance of lenvatinib in hepatocellular carcinoma by activating PI3K/AKT/LDHA signaling axis.Discover oncology · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Targeting Osteoclastogenesis: Sabutoclax reduces tumor-associated osteolysis and tumor burden within the bone microenvironment.American journal of cancer research · 2026Article
- Semaphorin 5A modulates focal adhesion pathway and lamellipodia formation in melanoma.Cell communication and signaling : CCS · 2025Article
- Bid Protein: A Participant in the Apoptotic Network with Roles in Viral Infections.International journal of molecular sciences · 2025Review
- Natural Products from Chinese Medicine Targeting NF-κB Signaling: Emerging Therapeutic Avenues for Neurodegenerative Diseases.Drug design, development and therapy · 2025Review
- Exploring the Potential of Chaihu-Danggui Tang in Breast Cancer Treatment Based on Network Pharmacology, Molecular Docking, and Experimental Validation.Breast cancer (Dove Medical Press) · 2025Article
- The Interplay between Autophagy and Mitochondria in Cancer.International journal of molecular sciences · 2024Review
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Authors and funding
12 authors.
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Abstract
introductionBcl-2 and Bcl-xL are the most studied anti-apoptotic members of Bcl-2 family proteins. We previously characterized both of them, not only for their role in regulating apoptosis and resistance to therapy in cancer cells, but also for their non-canonical functions, mainly including promotion of cancer progression, metastatization, angiogenesis, and involvement in the crosstalk among cancer cells and components of the tumor microenvironment. Our goal was to identify transcriptional signature and novel cellular pathways specifically modulated by Bcl-2.
methodsWe performed RNAseq analysis of siRNA-mediated transient knockdown of Bcl-2 or Bcl-xL in human melanoma cells and gene ontology analysis to identify a specific Bcl-2 transcriptional signature. Expression of genes modulated by Bcl-2 and associated to Hippo pathway were validated in human melanoma, breast adenocarcinoma and non-small cell lung cancer cell lines by qRT-PCR. Western blotting analysis were performed to analyse protein expression of upstream regulators of YAP and in relation to different level of Bcl-2 protein. The effects of YAP silencing in Bcl-2 overexpressing cancer cells were evaluated in migration and cell viability assays in relation to different stiffness conditions. In vitro wound healing assays and co-cultures were used to evaluate cancer-specific Bcl-2 ability to activate fibroblasts.
resultsWe demonstrated the Bcl-2-dependent modulation of Hippo Pathway in cancer cell lines from different tumor types by acting on upstream YAP regulators. YAP inhibition abolished the ability of Bcl-2 to increase tumor cell migration and proliferation on high stiffness condition of culture, to stimulate in vitro fibroblasts migration and to induce fibroblasts activation.
conclusionsWe discovered that Bcl-2 regulates the Hippo pathway in different tumor types, promoting cell migration, adaptation to higher stiffness culture condition and fibroblast activation. Our data indicate that Bcl-2 inhibitors should be further investigated to counteract cancer-promoting mechanisms.
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