Myoepithelial cells are unique hybrid cells that encase secretory glands, including mammary and salivary glands, converting genetic instructions into fluid movement and providing structural protection. These epithelial cells, which resemble smooth muscle, develop during the formation of glands and are positioned between the secretory luminal cells and the basement membrane. They arise during gland morphogenesis and remain essential for both secretion and defense. But their function goes far beyond support. Myoepithelial cells shape architecture, transmit contractile force, and serve as tumor suppressors in tissue microenvironments.
Contract and Construct
At the core of exocrine function lies a carefully choreographed contraction. Myoepithelial cells organize the contractile apparatus: α-smooth muscle actin (α-SMA) and myosin, to form actomyosin networks capable of generating mechanical force. Upon stimulation by neuromodulators like oxytocin or acetylcholine, these cells squeeze the secretory acini, reducing volume and propelling glandular contents outward [1]. The contraction is no isolated twitch; desmosomes and adherens junctions form a mechanical syncytium, coordinating the actomyosin pulses across the epithelium for gland-wide expulsion [2]. Studies in mouse models reveal that loss of ACTA2, the gene encoding α-SMA, impairs milk ejection during lactation, underscoring how essential this machinery is to function [3].
Engineer of Epithelial Structure
Rather than merely providing support, these cells create an architectural framework, comprising laminin, collagen IV, and various basement membrane components, that defines epithelial polarity and promotes ductal branching [4]. In the absence of this architectural guidance, luminal cells are unable to maintain their orientation and functionality.
Silent Enforcers of Epithelial Order
Long hailed as the body’s “natural tumor suppressors”, myoepithelial cells form both a physical and biochemical shield. These cells construct a dual barrier: physical scaffolding fortified by junctional proteins, and biochemical firepower in the form of protease inhibitors and anti-angiogenic factors [5]. What truly makes them unique is their vigilance and their proactive role in halting early cancer invasion by detecting and neutralizing aberrant behavior from adjacent luminal cells [6–7]. This function is lost or diminished in early breast cancer progression. The ability of myoepithelial cells to contain and sometimes reverse preneoplastic transformation has made them a central focus in cancer research.
Tailored Tasks
These cells are not mammary-specific. They are abundant in sweat, lacrimal, and even salivary glands, exhibiting tissue-specific shapes and dynamics [8–9]. In each location, they adapt their contractile architecture and matrix interactions to match gland function, from tear secretion to sweat release. This versatility across systems underscores their role as core regulators of exocrine physiology.
Forces and Feedback
Research demonstrates that contraction couples with adhesion through cadherin complexes, mechanical and molecular crosstalk that coordinates gland function and cell fate decisions [1]. These mechanochemical signals adapt to developmental stages and external demands. Their cytoskeletal organization is not entirely for cell migration; it transduces physical forces into alterations in gene expression, controlling tissue stiffness, gland branching, and regenerative destiny [5, 9–10]. New studies show that myoepithelial cells are even able to pass mechanical signals to adjacent stromal or immune cells, uniting gland behavior with overall tissue homeostasis [11].
New Roles, New Realms
Recent studies elucidate that myoepithelial cells don’t operate in absolutes. In certain contexts, like triple-negative breast cancers, they may undergo partial transitions into luminal-like states, blurring traditional lineage boundaries [11]. Their role as suppressors isn’t fixed either; under specific conditions, they may shift from guarding against tumors to quietly enabling them. With the rise of organoids and 3D culture systems, researchers are beginning to untangle how these dynamic cells influence not just cancer, but also tissue repair, longevity, and cellular identity over time [12–13]. Myoepithelial cells are not just muscle-like pumps; they serve as builders, watchmen, and active communicators. Their story is one of power, shape, and protection, reshaping glandular fluid movement and the integrity of tissues with each contraction.
Recognizing and appreciating the labs working in this space
- Garter Lab: UCSF, USA. https://gartnerlab.ucsf.edu/ FB: https://www.facebook.com/ucsfpharmacy
- Bissell Lab: Lawrence Berkeley National Lab, USA. https://www2.lbl.gov/LBL-Programs/lifesciences/BissellLab/main.html
- Ewald Lab: Johns Hopkins School of Medicine, USA https://cellbio.jhmi.edu/people/andrew-ewald-ph-d/
- Schedin Lab: OHSU, USA. https://www.ohsu.edu/school-of-medicine/schedin-lab, FB: https://www.facebook.com/OHSUedu, LinkedIn: https://www.linkedin.com/school/ohsu/
- Macara Lab: Vanderbilt University, USA. https://lab.vanderbilt.edu/macara-lab/
- LaBarge Lab: City of Hope, USA. https://www.cityofhope.org/research/beckman-research-institute/population-sciences/mark-labarge-lab, FB: https://www.facebook.com/cityofhope, Linkedin: https://www.linkedin.com/company/city-of-hope/, IG: @cityofhope, X: @cityofhope
- Mao Lab: Mass General/Harvard, USA. https://www.massgeneral.org/children/mucosal-immunology/faculty/mou-lab
- Cui Lab: Cedars Sinai Health Sciences University, USA. https://www.cedars-sinai.edu/health-sciences-university/research/labs/cui.html
- Larsen Lab: University at Albany, USA. https://larsenlab.org/, FB: https://www.facebook.com/universityatalbany, LinkedIn: https://www.linkedin.com/school/university-at-albany/, IG: @ualbany, X: @ualbany
- Zoukhari Lab: Tufts University, USA. https://dental.tufts.edu/people/faculty/driss-zoukhri, FB: https://www.facebook.com/TuftsDentalMedicine/, LinkedIn: https://www.linkedin.com/company/tufts-dental-school/, X: @Tuftsdental
References
- Adriance MC, Inman JL, Petersen OW, Bissell MJ. Myoepithelial cells: good fences make good neighbors. Breast Cancer Res. 2005;7(5):190. doi:10.1186/bcr1286
- Nakashima, K., Kato, H., Kurata, R. et al. Gap junction-mediated contraction of myoepithelial cells induces the peristaltic transport of sweat in human eccrine glands. Commun Biol 6, 1175 (2023). doi:10.1038/s42003–023–05557–9
- Haaksma CJ, Schwartz RJ, Tomasek JJ. Myoepithelial cell contraction and milk ejection are impaired in mammary glands of mice lacking smooth muscle alpha-actin. Biol Reprod. 2011;85(1):13–21. doi:10.1095/biolreprod.110.090639
- Bissell MJ, Bilder D. Polarity determination in breast tissue: desmosomal adhesion, myoepithelial cells, and laminin 1. Breast Cancer Res. 2003;5(2):117–119. doi:10.1186/bcr579
- Gudjonsson T, Adriance MC, Sternlicht MD, Petersen OW, Bissell MJ. Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia. J Mammary Gland Biol Neoplasia. 2005;10(3):261–272. doi:10.1007/s10911–005–9586–4
- Gudjonsson T, Ronnov-Jessen L, Villadsen R, Rank F, Bissell MJ, Petersen OW. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci. 2002;115(Pt 1):39–50. doi:10.1242/jcs.115.1.39
- Bissell MJ, Rizki A, Mian IS. Tissue architecture: the ultimate regulator of breast epithelial function. Curr Opin Cell Biol. 2003;15(6):753–762. doi:10.1016/j.ceb.2003.10.016
- Srivastava V, Huycke TR, Phong KT, Gartner ZJ. Organoid models for mammary gland dynamics and breast cancer. Curr Opin Cell Biol. 2020;66:51–58. doi:10.1016/j.ceb.2020.05.003
- Cerchiari A, Garbe JC, Todhunter ME, et al. Formation of spatially and geometrically controlled three-dimensional tissues in soft gels by sacrificial micromolding. Tissue Eng Part C Methods. 2015;21(6):541–547. doi:10.1089/ten.TEC.2014.0450
- Sirka OK, Shamir ER, Ewald AJ. Myoepithelial cells are a dynamic barrier to epithelial dissemination. J Cell Biol. 2018;217(10):3368–3381. doi:10.1083/jcb.201802144
- Shams A. Re-evaluation of the myoepithelial cells roles in the breast cancer progression. Cancer Cell Int. 2022;22(1):403. Published 2022 Dec 12. doi:10.1186/s12935–022–02829-y
- Lee, H.J., Myung, J.K., Kim, H.S. et al. Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers. Sci Rep 11, 17750 (2021). doi:10.1038/s41598–021–97351-y
- Kohler KT, Kim J, Villadsen R, Rønnov-Jessen L, Petersen OW. Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells. Breast Cancer Res. 2024;26(1):183. Published 2024 Dec 18. doi:10.1186/s13058–024–01939-x
About the author:
DR. CHRISTY KESTNER
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Christy Kestner holds a PhD in Neuroimmunology from the Medical University of South Carolina (MUSC), where she studied how complement drives pathological conditions related to neuroinflammation and brain injury (stroke and traumatic brain injury), as well as approaches to reduce harmful complement activation. She later conducted postdoctoral research in oncology therapeutic development, investigating new drug targets for pancreatic cancer. Dr. Kestner currently works as a scientific and medical writer, contributing op-eds to platforms such as STAT News and Newsweek, while also running her own science communication platform, Brain & Beyond, aimed at translating complex research into accessible content. Passionate about science storytelling, she is dedicated to making immunology and neuroscience both accurate and engaging for diverse audiences.
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Bruna received her Bachelor’s degree in Biological Sciences and her Master’s in Cellular and Molecular Biology from the University of Tuscia, Italy. She then pursued a PhD in Molecular Biology at the Max Planck Institute for Biology of Aging in Cologne, Germany.
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The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
