Overexpression of PELP1 in Lung Adenocarcinoma Promoted E 2 Induced Proliferation, Migration and Invasion of the Tumor Cells and Predicted a Worse Outcome of the Patients

• Published in: Pathology oncology research 2021-04, Vol.27, p.582443
• Main Authors: Zhang, Dongmei, Dai, Jiali, Pan, Yu, Wang, Xiuli, Qiao, Juanjuan, Sasano, Hironobu, Zhao, Baoshan, McNamara, Keely M, Guan, Xue, Liu, Lili, Zhang, Yanzhi, Chan, Monica S M, Cao, Shuwen, Liu, Ming, Song, Sihang, Wang, Lin
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Co-Repressor Proteins - genetics; Co-Repressor Proteins - metabolism; Estradiol - metabolism; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Female; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Survival Rate; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1532-2807
• DOI: 10.3389/pore.2021.582443

The expression of Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) has been reported to be dysregulated in non-small cell lung carcinoma, especially in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate the functional and prognostic roles of PELP1 in LUAD in this study. We first immunolocalized PELP1 in 76 cases of LUAD and 17 non-pathological or tumorous lung (NTL) tissue specimens and correlated the findings with the clinicopathological parameters of the patients. We then performed analysis including MTT, flow cytometry, wound healing, and transwell assays in order to further explore the biological roles of PELP1 in 17-β-estradiol (E ) induced cell proliferation, migration, and invasion of LUAD cells. We subsequently evaluated the prognostic significance of PELP1 in LUAD patients using the online survival analysis tool Kaplan-Meier Plotter. The status of PELP1 immunoreactivity in LUAD was significantly higher than that in the NTL tissues and significantly positively correlated with less differentiated features of carcinoma cells, positive lymph node metastasis, higher clinical stage as well as the status of ERα, ERβ, and PCNA. study did reveal that E promoted cell proliferation and migration and elevated PELP1 protein level in PELP1-high A549 and H1975 cells but not in PELP1-low H-1299 cells. Knock down of PELP1 significantly attenuated E induced cell proliferation, colony formation, cell cycle progress as well as migration and invasion of A549 and H1975 cells. Kaplan-Meier Plotter revealed that LUAD cases harboring higher PELP1 expression had significantly shorter overall survival. In summary, PELP1 played a pivotal role in the estrogen-induced aggressive transformation of LUAD and could represent adverse clinical outcome of the LUAD patients.