ArticleThe Journal of biological chemistry
The cell surface hyaluronidase TMEM2 regulates cell adhesion and migration via degradation of hyaluronan at focal adhesion sites.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- From permeation enhancer to therapeutic enabler: Advances, applications, and translational perspectives in hyaluronidase-based drug delivery.Materials today. Bio · 2026Review
- Glucocorticoid-Induced Proteome and Phosphoproteome Changes in Breast Cancer Cell Lines.Journal of proteome research · 2026Article
- Regulation of TMEM2-mediated hyaluronan degradation by CD44 and LYVE-1.Frontiers in molecular biosciences · 2026Article
- Association of LAMA3 expression with perineural invasion and chemoresistance in pancreatic ductal adenocarcinoma.Discover oncology · 2025Article
- Formulation Strategies for Immunomodulatory Natural Products in 3D Tumor Spheroids and Organoids: Current Challenges and Emerging Solutions.Pharmaceutics · 2025Review
- New molecules indispensable for hyaluronan degradation, HYBID (CEMIP/KIAA1199) and TMEM2 (CEMIP2): Differential roles in physiological and pathological non-neoplastic conditions.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Identifications of novel host cell factors that interact with the receptor-binding domain of the SARS-CoV-2 spike protein.The Journal of biological chemistry · 2024Article
- Proteomic profiling of tumour tissue-derived extracellular vesicles in colon cancer.Journal of extracellular biology · 2024Article
- Hepatotoxicity assessment of innovative nutritional supplements based on olive-oil formulations enriched with natural antioxidants.Frontiers in nutrition · 2024Article
- Article
- TMEM2 induces epithelial-mesenchymal transition and promotes resistance to temozolomide in GBM cells.Heliyon · 2023Article
- Hyaluronan in the Cancer Cells Microenvironment.Cancers · 2023Review
- Structure of the transmembrane protein 2 (TMEM2) ectodomain and its apparent lack of hyaluronidase activity.Wellcome open research · 2023Article
- Aggrecan and Hyaluronan: The Infamous Cartilage Polyelectrolytes - Then and Now.Advances in experimental medicine and biology · 2023Article
- Hyaluronan nanoscale clustering and Hyaluronan synthase 2 expression are linked to the invasion of child fibroblasts and infantile fibrosarcoma in vitro and in vivo.Scientific reports · 2022Article
- Expression and regulation of recently discovered hyaluronidases, HYBID and TMEM2, in chondrocytes from knee osteoarthritic cartilage.Scientific reports · 2022Article
- The cell surface hyaluronidase TMEM2 plays an essential role in mouse neural crest cell development and survival.PLoS genetics · 2022Article
- The Degradation of Hyaluronan in the Skin.Biomolecules · 2022Article
- Identification of Diagnostic Markers in Infantile Hemangiomas.Journal of oncology · 2022Article
- The cell surface hyaluronidase TMEM2 is essential for systemic hyaluronan catabolism and turnover.The Journal of biological chemistry · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The extracellular matrix (ECM) plays an important role in maintaining tissue homeostasis and poses a significant physical barrier to in vivo cell migration. Accordingly, as a means of enhancing tissue invasion, tumor cells use matrix metalloproteinases to degrade ECM proteins. However, the in vivo ECM is comprised not only of proteins but also of a variety of nonprotein components. Hyaluronan (HA), one of the most abundant nonprotein components of the interstitial ECM, forms a gel-like antiadhesive barrier that is impenetrable to particulate matter and cells. Mechanisms by which tumor cells penetrate the HA barrier have not been addressed. Here, we demonstrate that transmembrane protein 2 (TMEM2), the only known transmembrane hyaluronidase, is the predominant mediator of contact-dependent HA degradation and subsequent integrin-mediated cell-substrate adhesion. We show that a variety of tumor cells are able to eliminate substrate-bound HA in a tightly localized pattern corresponding to the distribution of focal adhesions (FAs) and stress fibers. This FA-targeted HA degradation is mediated by TMEM2, which itself is localized at site of FAs. TMEM2 depletion inhibits the ability of tumor cells to attach and migrate in an HA-rich environment. Importantly, TMEM2 directly binds at least two integrins via interaction between extracellular domains. Our findings demonstrate a critical role for TMEM2-mediated HA degradation in the adhesion and migration of cells on HA-rich ECM substrates and provide novel insight into the early phase of FA formation.
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Registered trials
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.