ArticleProceedings of the National Academy of Sciences of the United States of America2016
PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 84 citations in OpenAlex.
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- Lapatinib-Resistant HER2+ Breast Cancer Cells Are Associated with Dysregulation of MAPK and p70S6K/PDCD4 Pathways and Calcium Management, Influence of Cryptotanshinone.International journal of molecular sciences · 2025Article
- The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation.Communications biology · 2025Article
- Malignant tumor cells engender second membrane-lined organelles for self-protection and tumor progression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution.Cellular and molecular life sciences : CMLS · 2024Article
- Multidimensional Imaging of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Sodium regulates PLC and IPPhysiological reports · 2023Article
- Control of cell state transitions.Nature · 2022Article
- Pathophysiological role of ion channels and transporters in HER2-positive breast cancer.Cancer gene therapy · 2022Review
- 3D imaging for driving cancer discovery.The EMBO journal · 2022Review
- Active nNOS Is Required for Grp94-Induced Antioxidant Cytoprotection: A Lesson from Myogenic to Cancer Cells.International journal of molecular sciences · 2022Article
- Calcium Signalling in Breast Cancer Associated Bone Pain.International journal of molecular sciences · 2022Review
- Transcriptomic profiling reveals gene expression in human peripheral blood after exposure to low-dose ionizing radiation.Journal of radiation research · 2022Article
- Structure, Function and Regulation of the Plasma Membrane Calcium Pump in Health and Disease.International journal of molecular sciences · 2022Review
- Asporin Interacts With HER2 to Promote Thyroid Cancer MetastasisFrontiers in oncology · 2022Article
- MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells.Cell reports · 2021Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
In the lactating mammary gland, the plasma membrane calcium ATPase2 (PMCA2) transports milk calcium. Its expression is activated in breast cancers, where high tumor levels predict increased mortality. We find that PMCA2 expression correlates with HER2 levels in breast cancers and that PMCA2 interacts with HER2 in specific actin-rich membrane domains. Knocking down PMCA2 increases intracellular calcium, disrupts interactions between HER2 and HSP-90, inhibits HER2 signaling, and results in internalization and degradation of HER2. Manipulating PMCA2 levels regulates the growth of breast cancer cells, and knocking out PMCA2 inhibits the formation of tumors in mouse mammary tumor virus (MMTV)-Neu mice. These data reveal previously unappreciated molecular interactions regulating HER2 localization, membrane retention, and signaling, as well as the ability of HER2 to generate breast tumors, suggesting that interactions between PMCA2 and HER2 may represent therapeutic targets for breast cancer.
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