Proteasome 26s subunit, non-atpase 3 (Psmd3) regulates breast cancer by stabilizing her2 from degradation

Abdulfattah Salah Fararjeh, Li Ching Chen, Yuan Soon Ho, Tzu Chun Cheng, Yun Ru Liu, Hang Lung Chang, Hui Wen Chang, Chih Hsiung Wu, Shih Hsin Tu

Research output: Contribution to journalArticle

Abstract

It is well-known that human epidermal growth factor receptor 2 (HER2) is critical for breast cancer (BC) development and progression. Several studies have revealed the role of the ubiquitin/proteasome system (UPS) in cancer. In this study, we investigated the expression level of Proteasome 26S subunit, non-ATPase 3 (PSMD3) in BC using BC cell lines, human BC tissue samples, Oncomine, and TCGA databases and studied the PSMD3-HER2 protein interaction. PSMD3 was upregulated in BC, particularly in the HER2+ subtype. PSMD3 immunostaining was detected in the cytoplasm and nucleus of BC tumor tissues. Strong interaction between PSMD3 and HER2 at the protein level was observed. Knockdown of PSMD3 significantly impaired the stability of HER2, inhibited BC cell proliferation and colony formation, and induced cell apoptosis. Ubiquitination process was strongly enhanced after knockdown of PSMD3 in association with decreased HER2 level. Accumulation and Localization of LAMP-1 in the cell membrane with decreased HER2 immunostaining was observed after knockdown of PSMD3. High expression level of PSMD3 was associated with HER2 expression (p < 0.001), tumor size (p < 0.001), and clinical stage (p = 0.036). High expression level of PSMD3 predicted a short overall survival (OS), particularly for HER2+. Overall, we provide a novel function for PSMD3 in stabilizing HER2 from degradation in HER2+ BC, which suggests that PSMD3 is a novel target for HER2+ BC.

Original languageEnglish
Article number527
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

Fingerprint

Breast Neoplasms
human ERBB2 protein
ATP dependent 26S protease
Ubiquitination
Proteasome Endopeptidase Complex
Ubiquitin
Neoplasms
Cytoplasm
Proteins
Cell Proliferation
Cell Membrane
Databases
Apoptosis
Cell Line
Survival

Keywords

  • Breast cancer
  • Human epidermal growth factor receptor 2 (HER2)
  • Non-ATPase 3 (PSMD3)
  • Proteasome 26S subunit
  • Ubiquitination

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Proteasome 26s subunit, non-atpase 3 (Psmd3) regulates breast cancer by stabilizing her2 from degradation. / Fararjeh, Abdulfattah Salah; Chen, Li Ching; Ho, Yuan Soon; Cheng, Tzu Chun; Liu, Yun Ru; Chang, Hang Lung; Chang, Hui Wen; Wu, Chih Hsiung; Tu, Shih Hsin.

In: Cancers, Vol. 11, No. 4, 527, 01.04.2019.

Research output: Contribution to journalArticle

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abstract = "It is well-known that human epidermal growth factor receptor 2 (HER2) is critical for breast cancer (BC) development and progression. Several studies have revealed the role of the ubiquitin/proteasome system (UPS) in cancer. In this study, we investigated the expression level of Proteasome 26S subunit, non-ATPase 3 (PSMD3) in BC using BC cell lines, human BC tissue samples, Oncomine, and TCGA databases and studied the PSMD3-HER2 protein interaction. PSMD3 was upregulated in BC, particularly in the HER2+ subtype. PSMD3 immunostaining was detected in the cytoplasm and nucleus of BC tumor tissues. Strong interaction between PSMD3 and HER2 at the protein level was observed. Knockdown of PSMD3 significantly impaired the stability of HER2, inhibited BC cell proliferation and colony formation, and induced cell apoptosis. Ubiquitination process was strongly enhanced after knockdown of PSMD3 in association with decreased HER2 level. Accumulation and Localization of LAMP-1 in the cell membrane with decreased HER2 immunostaining was observed after knockdown of PSMD3. High expression level of PSMD3 was associated with HER2 expression (p < 0.001), tumor size (p < 0.001), and clinical stage (p = 0.036). High expression level of PSMD3 predicted a short overall survival (OS), particularly for HER2+. Overall, we provide a novel function for PSMD3 in stabilizing HER2 from degradation in HER2+ BC, which suggests that PSMD3 is a novel target for HER2+ BC.",
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AU - Fararjeh, Abdulfattah Salah

AU - Chen, Li Ching

AU - Ho, Yuan Soon

AU - Cheng, Tzu Chun

AU - Liu, Yun Ru

AU - Chang, Hang Lung

AU - Chang, Hui Wen

AU - Wu, Chih Hsiung

AU - Tu, Shih Hsin

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AB - It is well-known that human epidermal growth factor receptor 2 (HER2) is critical for breast cancer (BC) development and progression. Several studies have revealed the role of the ubiquitin/proteasome system (UPS) in cancer. In this study, we investigated the expression level of Proteasome 26S subunit, non-ATPase 3 (PSMD3) in BC using BC cell lines, human BC tissue samples, Oncomine, and TCGA databases and studied the PSMD3-HER2 protein interaction. PSMD3 was upregulated in BC, particularly in the HER2+ subtype. PSMD3 immunostaining was detected in the cytoplasm and nucleus of BC tumor tissues. Strong interaction between PSMD3 and HER2 at the protein level was observed. Knockdown of PSMD3 significantly impaired the stability of HER2, inhibited BC cell proliferation and colony formation, and induced cell apoptosis. Ubiquitination process was strongly enhanced after knockdown of PSMD3 in association with decreased HER2 level. Accumulation and Localization of LAMP-1 in the cell membrane with decreased HER2 immunostaining was observed after knockdown of PSMD3. High expression level of PSMD3 was associated with HER2 expression (p < 0.001), tumor size (p < 0.001), and clinical stage (p = 0.036). High expression level of PSMD3 predicted a short overall survival (OS), particularly for HER2+. Overall, we provide a novel function for PSMD3 in stabilizing HER2 from degradation in HER2+ BC, which suggests that PSMD3 is a novel target for HER2+ BC.

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