ArticleBMC cancer2015
Targeting connexin 43 with α-connexin carboxyl-terminal (ACT1) peptide enhances the activity of the targeted inhibitors, tamoxifen and lapatinib, in breast cancer: clinical implication for ACT1.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Oral connexin43-peptide-loaded milk extracellular vesicles mitigate lethal radiation injury while preserving tumour radiosensitivity.Cancer letters · 2026Article
- Nanoencapsulated senotherapeutic compounds targeting connexin-43 for enhanced wound healing.iScience · 2026Article
- Simvastatin Enhances the Cytotoxic Effects of Doxorubicin in a Mammary Adenocarcinoma Cell Model by Involving Connexin 43.Journal of biochemical and molecular toxicology · 2025Article
- Review
- Pannexins in the musculoskeletal system: new targets for development and disease progression.Bone research · 2024Review
- Article
- Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer.Cancers · 2024Article
- Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer.Molecular cancer therapeutics · 2024Article
- Correlation between connexin 43 expression in circulating tumor cells and biological characteristics of breast cancer.Heliyon · 2023Article
- The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis.Antioxidants (Basel, Switzerland) · 2023Review
- The roles of connexins and gap junctions in the progression of cancer.Cell communication and signaling : CCS · 2023Review
- Mechanisms of Connexin Regulating Peptides.International journal of molecular sciences · 2021Review
- Connexin therapeutics: blocking connexin hemichannel pores is distinct from blocking pannexin channels or gap junctions.Neural regeneration research · 2021Review
- Effects of Alpha-Connexin Carboxyl-Terminal Peptide (aCT1) and Bowman-Birk Protease Inhibitor (BBI) on Canine Oral Mucosal Melanoma (OMM) Cells.Frontiers in veterinary science · 2021Article
- Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway.International journal of biological sciences · 2021Article
- Connexins in Cancer: Jekyll or Hyde?Biomolecules · 2020Review
- Connexins-Therapeutic Targets in Cancers.International journal of molecular sciences · 2020Review
- Connexins in cancer: bridging the gap to the clinic.Oncogene · 2019Review
- Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTreatment failure is a critical issue in breast cancer and identifying useful interventions that optimize current cancer therapies remains a critical unmet need. Expression and functional studies have identified connexins (Cxs), a family of gap junction proteins, as potential tumor suppressors. Studies suggest that Cx43 has a role in breast cancer cell proliferation, differentiation, and migration. Although pan-gap junction drugs are available, the lack of specificity of these agents increases the opportunity for off target effects. Consequently, a therapeutic agent that specifically modulates Cx43 would be beneficial and has not been tested in breast cancer. In this study, we now test an agent that specifically targets Cx43, called ACT1, in breast cancer.
methodsWe evaluated whether direct modulation of Cx43 using a Cx43-directed therapeutic peptide, called ACT1, enhances Cx43 gap junctional activity in breast cancer cells, impairs breast cancer cell proliferation or survival, and enhances the activity of the targeted inhibitors tamoxifen and lapatinib.
resultsOur results show that therapeutic modulation of Cx43 by ACT1 maintains Cx43 at gap junction sites between cell-cell membrane borders of breast cancer cells and augments gap junction activity in functional assays. The increase in Cx43 gap junctional activity achieved by ACT1 treatment impairs proliferation or survival of breast cancer cells but ACT1 has no effect on non-transformed MCF10A cells. Furthermore, treating ER+ breast cancer cells with a combination of ACT1 and tamoxifen or HER2+ breast cancer cells with ACT1 and lapatinib augments the activity of these targeted inhibitors.
conclusionsBased on our findings, we conclude that modulation of Cx43 activity in breast cancer can be effectively achieved with the agent ACT1 to sustain Cx43-mediated gap junctional activity resulting in impaired malignant progression and enhanced activity of lapatinib and tamoxifen, implicating ACT1 as part of a combination regimen in breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.