Overexpression of HMGA2 in breast cancer promotes cell proliferation, migration, invasion and stemness
- 3 March 2020
- journal article
- research article
- Published by Taylor & Francis Ltd in Emerging Therapeutic Targets
- Vol. 24 (3), 255-265
- https://doi.org/10.1080/14728222.2020.1736559
Abstract
Despite improved therapeutic strategies for early-stage breast cancer, the most common cancer type in women, relapse remains common and the underlying mechanisms for this progression remain poorly understood. To gain more insight, we studied the DNA-binding protein HMGA2 in breast cancer development and stemness. We demonstrated that HMGA2 is overexpressed in breast cancer tissues at the mRNA and protein levels (P value <0.0001). HMGA2 knockdown and overexpression in breast cancer cells revealed that HMGA2 promotes cell proliferation and protects against apoptosis via the intrinsic pathway. HMGA2 knockdown also causes cell cycle arrest in G2/M phase. In addition, we found that HMGA2 increases breast cancer cell migration and invasion (P value <0.001) and promotes the acquisition of cancer stem cell features, both in vitro, in colony formation (P value <0.01) and spheroid assays, and in breast cancer tissues. Overexpression of HMGA2 in breast cancer spurs the acquisition of several hallmarks of cancer, including increased cell proliferation, migration, invasion and stemness, and decreased apoptosis. Thus, targeting HMGA2 could represent an effective strategy to block breast cancer progression.Keywords
This publication has 36 references indexed in Scilit:
- High Mobility Group A Proteins as Tumor MarkersFrontiers in Medicine, 2015
- Connecting the coronaries: How the coronary plexus develops and is functionalizedDevelopmental Biology, 2014
- HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasisProceedings of the National Academy of Sciences of the United States of America, 2013
- The Role of Cancer Stem Cells in Breast Cancer Initiation and Progression: Potential Cancer Stem Cell-Directed TherapiesThe Oncologist, 2012
- Ablation of Breast Cancer Stem Cells with RadiationTranslational Oncology, 2011
- Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesisGenes & Development, 2009
- HMGA2 and Smads Co-regulate SNAIL1 Expression during Induction of Epithelial-to-Mesenchymal TransitionOnline Journal of Public Health Informatics, 2008
- Intrinsic Resistance of Tumorigenic Breast Cancer Cells to ChemotherapyJNCI Journal of the National Cancer Institute, 2008
- HMGA2 overexpression in non‐small cell lung cancerMolecular Carcinogenesis, 2007
- Prospective identification of tumorigenic breast cancer cellsProceedings of the National Academy of Sciences of the United States of America, 2003