Cellular and molecular evaluation of ANKHD1 silencing in breast cancer

• Grant number: 19/25421-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2020
• End date: June 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: João Agostinho Machado Neto
• Grantee: Bruna Oliveira de Almeida
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Although widely studied, the molecular basis of breast cancer is still unclear, and the relevance of identifying new molecular markers and signaling pathways that may be useful in prognostic stratification, predicting response to therapy, and developing breast cancer new therapeutic options is evident. In this sense, the Ankyrin Repeat and KH Domain Containing 1 protein, ANKHD1, has been identified as important for the proliferation, migration and invasion of neoplastic cells. ANKHD1 is a protein with 20 ankyrin repeats and a single K homology (KH) domain, suggesting its role as a scaffold protein in important signaling pathways and cellular interactions. In fact, interactions between ANKHD1 and other proteins, such as YAP1, SIVA1, SHP2, p21 and SMYD3, has been described in several types of cancer. Moreover, recently, ANKHD1 has been related to the regulation of JAK2 / STAT pathway activation. In breast cancer, its prognostic impact on patients was initially described. In these patients, high expression of ANKHD1 was associated with worse prognosis. The purpose of this research project is to investigate and characterize the effect of ANKHD1 inhibition on breast cancer cells evaluating protein and gene expression of related proteins, proliferation, migration and apoptosis. To this end, we will use well-established models of neoplastic breast cell lines, as well as cell and molecular biology techniques, including siRNA transfection inhibition, quantitative PCR, Western Blotting and proliferation, migration and apoptosis assays. We hope these findings will pave the way for further investigations into the cellular functions of ANKHD1 in breast cancer. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LIMA, KELI; DE MIRANDA, LIVIA BASSANI LINS; GARNIQUE, ANALI DEL MILAGRO BERNABE; DE ALMEIDA, BRUNA OLIVEIRA; DO NASCIMENTO, MARIANE CRISTINA; ALCANTARA, GUILHERME AUGUSTO SOUSA; MACHADO-SANTELLI, GLAUCIA MARIA; REGO, EDUARDO MAGALHAES; MACHADO-NETO, JOAO AGOSTINHO. The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells. CANCERS, v. 15, n. 15, p. 14-pg., 2023-08-01. (19/23864-7, 21/11606-3, 20/12842-0, 22/03316-8, 19/25421-5)

DE ALMEIDA, BRUNA OLIVEIRA; MACHADO-NETO, JOAO AGOSTINHO. Emerging functions for ANKHD1 in cancer-related signaling pathways and cellular processes. BMB REPORTS, v. 53, n. 8, p. 413-418, AUG 31 2020. (17/24993-0, 19/23864-7, 19/25421-5)