Hyaluronan synthase 2 (HAS2) regulates cell phenotype and invadopodia formation in luminal-like breast cancer cells
| Autor: | Guoliang Zhang, Yiqing He, Feng Gao, Yan Du, Manlin Cao, Cuixia Yang, Yumeng Sheng, Yiwen Liu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
endocrine system Clinical Biochemistry Motility Apoptosis Breast Neoplasms Vimentin Mice SCID Matrix metalloproteinase Hyaluronan Synthase 2 Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Mice Inbred NOD Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans Neoplasm Invasiveness Molecular Biology Cell Proliferation Gene knockdown biology Chemistry Cell Biology General Medicine medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Podosomes Invadopodia biology.protein Cancer research Female Hyaluronan Synthases Cortactin |
| Zdroj: | Molecular and Cellular Biochemistry. 476:3383-3391 |
| ISSN: | 1573-4919 0300-8177 |
| DOI: | 10.1007/s11010-021-04165-7 |
| Popis: | Although luminal breast cancer cells are typically highly cohesive epithelial cells and have low invasive ability, many eventually develop metastasis. Until now, the underlying mechanisms remain obscure. In this work, we showed that the level of hyaluronic acid synthase 2 (HAS2) was positively correlated with the malignant phenotype of breast cancer cells. Notably, the increased expression of HAS2 promoted the invasive and migratory abilities of luminal breast cancer cells in vitro, followed by a reduced expression of E-cadherin, β-catenin, and ZO-1, and an elevated expression of N-cadherin and vimentin. Furthermore, overexpression of HAS2 promoted while knockdown of HAS2 impeded invadopodia formation, which subsequently increased or decreased the activation of cortactin, Tks5, and metalloproteinases (MMPs). Activation of these invadopodia-related proteins was prevented by inhibition of HAS2 or disruption of HA, which in turn attenuated the increased motility and invasiveness. Further, in vivo study showed that, HAS2 increased tumor growth and the rate of lung metastasis via driving transition to an invasive cell phenotype in SCID mice that were orthotopically transplanted with luminal breast cancer cells. Collectively, our results showed that HAS2 promoted cell invasion by inducing transition to an invasive phenotype and by enhancing invadopodia formation in luminal breast cancer cells, which may provide new mechanistic insights into its role in tumor metastasis. |
| Databáze: | OpenAIRE |
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