Cancers: Global Genomic and Proteomic Analysis Identified Critical Pathways Modulated by Proto-Oncogene PELP1 in TNBC (Chen & Lai)

Published On: February 25, 2022
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by Zexuan Liu 1,2,†,Kristin A. Altwegg 1,3,†ORCID,Junhao Liu 1,2,Susan T. Weintraub 4,Yidong Chen 5,6,Zhao Lai 5,7,Gangadhara R. Sareddy 1,3,Suryavathi Viswanadhapalli 1,3,*ORCID and Ratna K. Vadlamudi 1,3,8,*

Simple Summary

The proto-oncogene PELP1 is commonly overexpressed in many cancers including triple-negative breast cancer (TNBC). In this study, we utilized global proteomic and RNA-seq approaches to elucidate the molecular mechanisms by which PELP1 contributes to the progression of TNBC. Global quantitative proteome analysis revealed that the oncogenic activities of PELP1 involve regulation of the expression of ribosomal proteins, as well as ribosomal regulatory complexes. RNA-seq studies discovered that PELP1 modulates the functions of c-Myc in TNBC, which is a known regulator of ribosomal proteins. Furthermore, TCGA-TNBC data confirmed PELP1 has high expression in TNBC, and this pattern exhibited a positive correlation with c-Myc and regulators of ribosomal proteins. Collectively, our studies suggest that PELP1 contributes to TNBC progression by modulation of ribosome biogenesis pathways.

Abstract

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 approach. TCGA data sets were utilized to determine the status of PELP1 in TNBC patient tumors and examine 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 the regulation of the 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 the cell cycle, apoptosis, and ribosome biogenesis pathways.

Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.

 

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Article Categories: Research Paper

Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.

Stay connected with the Greehey CCRI on Facebook, Twitter, LinkedIn, and Instagram.