{"entity": "publication", "iuid": "432fc2cd8bc3421ead2aa4e26b3a925e", "timestamp": "2026-08-29T04:15:56.707Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/432fc2cd8bc3421ead2aa4e26b3a925e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/432fc2cd8bc3421ead2aa4e26b3a925e"}}, "title": "Has2 natural antisense RNA and Hmga2 promote Has2 expression during TGF\u03b2-induced EMT in breast cancer.", "authors": [{"family": "Kolliopoulos", "given": "Constantinos", "initials": "C"}, {"family": "Lin", "given": "Chun-Yu", "initials": "CY"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A"}, {"family": "Heldin", "given": "Paraskevi", "initials": "P"}], "type": "journal article", "published": "2019-07-00", "journal": {"title": "Matrix Biol.", "issn": "1569-1802", "volume": "80", "pages": "29-45", "issn-l": "0945-053X"}, "abstract": "The glycosaminoglycan hyaluronan has a crucial role in tissue organization and cell signaling. Hyaluronan accumulates in conjunction with rapid tissue remodeling during embryogenesis, as well as in inflammatory conditions and cancer. We report a negative correlation between the expression of genes encoding hyaluronan synthase HAS2, its natural antisense transcript HAS2-AS, the chromatin modulating factor HMGA2 and transforming growth factor-\u03b2 (TGF\u03b2), and survival of patients with invasive breast carcinomas. In mouse mammary epithelial cells, TGF\u03b2 activates Smad and non-Smad signaling pathways, resulting in the transcriptional induction of Has2, Has2as (the mouse ortholog of HAS2-AS) and Hmga2, as well as epithelial-mesenchymal transition (EMT)-promoting transcription factors, such as Snail. Importantly, Has2as abrogation suppressed the TGF\u03b2 induction of EMT markers, including Snai1, Hmga2, Fn1, and suppressed the mesenchymal phenotype. TGF\u03b2 induction of Hmga2, Has2as and Has2, and synthesis of hyaluronan were accompanied with activation of Akt and Erk1/2 MAP-kinase signaling and were required for breast cancer cell motility. Importantly, the hyaluronan receptor Cd44, but not Hmmr, was required for TGF\u03b2-mediated EMT phenotype. Interestingly, Has2as was found to contribute to the maintenance of stem cell factors and breast cancer stemness. Our findings show that Has2as has a key role in TGF\u03b2- and HAS2-induced breast cancer EMT, migration and acquisition of stemness.", "doi": "10.1016/j.matbio.2018.09.002", "pmid": "30194979", "labels": [], "xrefs": [{"db": "pii", "key": "S0945-053X(18)30196-3"}], "notes": [], "created": "2026-08-20T08:00:27.789Z", "modified": "2026-08-20T08:00:27.840Z"}