Global Genomic and Proteomic Analysis Identified Critical Pathways Modulated by Proto-Oncogene PELP1 in TNBC

Zexuan Liu, Kristin A. Altwegg, Junhao Liu, Susan T. Weintraub, Yidong Chen, Zhao Lai, Gangadhara R. Sareddy, Suryavathi Viswanadhapalli, Ratna K. Vadlamudi

Producción científica: Articlerevisión exhaustiva

6 Citas (Scopus)

Resumen

The PELP1 oncogene is commonly overexpressed in many cancers, including triple negative breast cancer (TNBC). However, the mechanisms by which PELP1 contributes to TNBC progression are not well understood. To elucidate these mechanisms, we generated CRISPR-Cas9 mediated PELP1 knockout TNBC cell lines, and alterations in the proteome were examined using global data-independent acquisition mass spectrometry (DIA-MS). Further mechanistic studies utilized shRNA knockdown, Western blotting, and RNA-seq approaches. TCGA data sets were utilized for determining the status of PELP1 in TNBC patient tumors and for examining its correlation with ribosomal proteins. Global DIA-MS studies revealed that 127 proteins are upregulated while 220 proteins are downregulated upon PELP1-KO. Bioinformatic analyses suggested that the oncogenic activities of PELP1 involve regulation of expression of ribosomal proteins and ribosomal complexes. RNA-seq studies further suggested PELP1 modulates the functions of transcription factor c-Myc in TNBC. TCGA data confirmed PELP1 has high expression in TNBC patient tumors, and this high expression pattern correlates with c-Myc, a regulator of ribosomal proteins. Collectively, our global approach studies suggest that PELP1 contributes to TNBC progression by modulation of cell cycle, apoptosis, and ribosome biogenesis pathways.

Idioma originalEnglish (US)
Número de artículo930
PublicaciónCancers
Volumen14
N.º4
DOI
EstadoPublished - feb 1 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Huella

Profundice en los temas de investigación de 'Global Genomic and Proteomic Analysis Identified Critical Pathways Modulated by Proto-Oncogene PELP1 in TNBC'. En conjunto forman una huella única.

Citar esto