ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer
Communication between the endoplasmic reticulum (ER) and mitochondria through mitochondria-associated ER membranes (MAMs) is assisted by tethering proteins and signaling pathways, manifesting the dynamic exchange of lipids, calcium, and signaling molecules. However, dysregulation of tethering and si...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329925000645 |
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| author | Chamanthi Paidi Yerusha Nuthalapati Anuveda Sree Samudrala Priyamvada Bhamidipati Charanteja Mangam Danny R. Welch Ganji Purnachandra Nagaraju RamaRao Malla |
| author_facet | Chamanthi Paidi Yerusha Nuthalapati Anuveda Sree Samudrala Priyamvada Bhamidipati Charanteja Mangam Danny R. Welch Ganji Purnachandra Nagaraju RamaRao Malla |
| author_sort | Chamanthi Paidi |
| collection | DOAJ |
| description | Communication between the endoplasmic reticulum (ER) and mitochondria through mitochondria-associated ER membranes (MAMs) is assisted by tethering proteins and signaling pathways, manifesting the dynamic exchange of lipids, calcium, and signaling molecules. However, dysregulation of tethering and signaling proteins contributes to the progression of breast cancer (BC). Abnormal MAM structures and altered ER-mitochondrial tethering impair mitochondrial functions and thereby drive BC progression. Altered mitochondrial dynamics, often characterized by dysregulated dynamin-related protein 1 (Drp1) and mitofusin-2 (Mfn2) activity, enhances BC cell survival. Similarly, ER stress and the unfolded protein response, both modulated by dysregulated ER-mitochondrial contacts, promote drug resistance. In BC, caveolae-dependent and -independent caveolin-1 signaling alongside Yes-associated protein (YAP) signaling pathway alters organelle dynamics by interacting with Drp1 and Mfn2, underscoring their therapeutic potential. This review explores potential therapeutic strategies targeting ER-mitochondrial communications and their potential for hindering BC progression. These strategies include modulating mitochondrial dynamics and promoting controlled ER stress by disrupting aberrant ER-mitochondrial tethering using chemotherapeutics, clinical inhibitors, and natural compounds, alone or in combination. Ultimately, targeting dysregulated ER-mitochondrial tethering has significant potential to improve patient outcomes in BC. |
| format | Article |
| id | doaj-art-c5e10e85eef7418fa930a15189a1fb74 |
| institution | OA Journals |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-c5e10e85eef7418fa930a15189a1fb742025-08-20T02:26:57ZengElsevierMolecular Therapy: Oncology2950-32992025-06-0133220099510.1016/j.omton.2025.200995ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancerChamanthi Paidi0Yerusha Nuthalapati1Anuveda Sree Samudrala2Priyamvada Bhamidipati3Charanteja Mangam4Danny R. Welch5Ganji Purnachandra Nagaraju6RamaRao Malla7Cancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, IndiaCancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, IndiaCancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, IndiaCancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, IndiaCancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, IndiaDepartment of Cancer Biology and University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USASchool of Medicine, Division of Hematology and Oncology, University of Alabama, Birmingham, AL 35233, USACancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, India; Corresponding author: RamaRao Malla, Cancer Biology Group, Cancer Biology Laboratory, Department of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, India.Communication between the endoplasmic reticulum (ER) and mitochondria through mitochondria-associated ER membranes (MAMs) is assisted by tethering proteins and signaling pathways, manifesting the dynamic exchange of lipids, calcium, and signaling molecules. However, dysregulation of tethering and signaling proteins contributes to the progression of breast cancer (BC). Abnormal MAM structures and altered ER-mitochondrial tethering impair mitochondrial functions and thereby drive BC progression. Altered mitochondrial dynamics, often characterized by dysregulated dynamin-related protein 1 (Drp1) and mitofusin-2 (Mfn2) activity, enhances BC cell survival. Similarly, ER stress and the unfolded protein response, both modulated by dysregulated ER-mitochondrial contacts, promote drug resistance. In BC, caveolae-dependent and -independent caveolin-1 signaling alongside Yes-associated protein (YAP) signaling pathway alters organelle dynamics by interacting with Drp1 and Mfn2, underscoring their therapeutic potential. This review explores potential therapeutic strategies targeting ER-mitochondrial communications and their potential for hindering BC progression. These strategies include modulating mitochondrial dynamics and promoting controlled ER stress by disrupting aberrant ER-mitochondrial tethering using chemotherapeutics, clinical inhibitors, and natural compounds, alone or in combination. Ultimately, targeting dysregulated ER-mitochondrial tethering has significant potential to improve patient outcomes in BC.http://www.sciencedirect.com/science/article/pii/S2950329925000645MT: Regular Issuebreast cancercaveolin-1ER-mitochondria tetheringROSYAP |
| spellingShingle | Chamanthi Paidi Yerusha Nuthalapati Anuveda Sree Samudrala Priyamvada Bhamidipati Charanteja Mangam Danny R. Welch Ganji Purnachandra Nagaraju RamaRao Malla ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer Molecular Therapy: Oncology MT: Regular Issue breast cancer caveolin-1 ER-mitochondria tethering ROS YAP |
| title | ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer |
| title_full | ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer |
| title_fullStr | ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer |
| title_full_unstemmed | ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer |
| title_short | ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer |
| title_sort | er mitochondria tethering and its signaling a novel therapeutic target in breast cancer |
| topic | MT: Regular Issue breast cancer caveolin-1 ER-mitochondria tethering ROS YAP |
| url | http://www.sciencedirect.com/science/article/pii/S2950329925000645 |
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