PHLDA1 (pleckstrin homology-like domain, family A, member 1) knockdown promotes migration and invasion of MCF10A breast epithelial cells

Autor(es)

Bonatto, Naieli ^{[1, 2]} ; Carlini, Maria Jose ^{[1, 2]} ; de Bessa Garcia, Simone Aparecida ^{[1, 2]} ; Nagai, Maria Aparecida ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Radiol & Oncol, Discipline Oncol, Fac Med, Sao Paulo - Brazil

^[2] Canc Inst Sao Paulo, Ctr Translat Res Oncol, Lab Mol Genet, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELL ADHESION & MIGRATION; v. 12, n. 1, p. 37-46, 2018.
• Citações Web of Science: 1

Resumo

PHLDA1 (pleckstrin homology-like domain, family A, member 1) is a multifunctional protein that plays distinct roles in several biological processes including cell death and therefore its altered expression has been identified in different types of cancer. Progressively loss of PHLDA1 was found in primary and metastatic melanoma while its overexpression was reported in intestinal and pancreatic tumors. Previous work from our group showed that negative expression of PHLDA1 protein was a strong predictor of poor prognosis for breast cancer disease. However, the function of PHLDA1 in mammary epithelial cells and the tumorigenic process of the breast is unclear. To dissect PHLDA1 role in human breast epithelial cells, we generated a clone of MCF10A cells with stable knockdown of PHLDA1 and performed functional studies. To achieve reduced PHLDA1 expression we used shRNA plasmid transfection and then changes in cell morphology and biological behavior were assessed. We found that PHLDA1 downregulation induced marked morphological alterations in MCF10A cells, such as changes in cell-to-cell adhesion pattern and cytoskeleton reorganization. Regarding cell behavior, MCF10A cells with reduced expression of PHLDA1 showed higher proliferative rate and migration ability in comparison with control cells. We also found that MCF10A cells with PHLDA1 knockdown acquired invasive properties, as evaluated by transwell Matrigel invasion assay and showed enhanced colony-forming ability and irregular growth in low attachment condition. Altogether, our results indicate that PHLDA1 downregulation in MCF10A cells leads to morphological changes and a more aggressive behavior. (AU)

• Processo FAPESP: 15/10208-3 - Papel funcional dos genes PHLDA1, RET, BCAR3 e da isoforma A do Receptor de Progesterona (PRA) no câncer de mama: implicações clínicas
• Beneficiário: Maria Aparecida Nagai
• Modalidade de apoio: Auxílio à Pesquisa - Regular