Knockdown of ribosomal protein S6 suppresses proliferation, migration, and invasion in epithelial ovarian cancer

Yang, Xueqing; Xu, Luxi; Yang, Yongmei; Xiong, Chang; Yu, Jinjin; Wang, Yuan; Lin, Yaying

doi:10.1186/s13048-020-00707-7

Cited by 21 publications

(26 citation statements)

References 30 publications

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“…Additionally, the retinoblastoma-associated protein (RB) might contribute to the transcriptional upregulation of RPS6 by binding to E2F1 on the RPS6 promoter. RPS6 -knockdown (KD) is known to downregulate phospho (p)-RB in various cancer cells [ 37 , 38 , 39 , 40 ]; however, it is elusive whether such a positive feedback loop between RPS6 and the p-RB level is involved in cancer progression. Furthermore, the precise roles and effects of E2F1 and RB on the transcription of RPS6 remain to be determined.…”

Section: Regulation Of Rps6mentioning

confidence: 99%

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Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

You

Park

et al. 2021

IJMS

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Ribosomal protein S6 (RPS6) is a component of the 40S small ribosomal subunit and participates in the control of mRNA translation. Additionally, phospho (p)-RPS6 has been recognized as a surrogate marker for the activated PI3K/AKT/mTORC1 pathway, which occurs in many cancer types. However, downstream mechanisms regulated by RPS6 or p-RPS remains elusive, and the therapeutic implication of RPS6 is underappreciated despite an approximately half a century history of research on this protein. In addition, substantial evidence from RPS6 knockdown experiments suggests the potential role of RPS6 in maintaining cancer cell proliferation. This motivates us to investigate the current knowledge of RPS6 functions in cancer. In this review article, we reviewed the current information about the transcriptional regulation, upstream regulators, and extra-ribosomal roles of RPS6, with a focus on its involvement in cancer. We also discussed the therapeutic potential of RPS6 in cancer.

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Section: Regulation Of Rps6mentioning

confidence: 99%

“…Functional implications of RPS6 in cell cycle regulation were also demonstrated by RPS6 -KD in a variety of cancer cells. RPS6 -KD induced G 0 /G 1 cell cycle-arrest in human NSCLC cells [ 37 , 38 ], ovarian cancer cells [ 40 ], and drug-resistant melanoma cells [ 39 ] (see Section 5.2 . RPS6-KD in Cancer Cells).…”

Section: Functions Of Rps6mentioning

confidence: 99%

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

You

Park

et al. 2021

IJMS

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“…Previous publications have demonstrated the importance of ribosomal proteins in ovarian cancer. Knockdown of RPS6 resulted in an inhibition of ovarian cancer cell proliferation and invasion [ 30 ]. Similarly, the metabolic pathways have been shown to be pivotal for the development of ovarian and other cancers [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer

Ulm

Redfern

Wilson

et al. 2020

JPM

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Objective: The objective of this study is to identify and validate novel therapeutic target(s) in ovarian cancer. Background: Development of targeted therapeutics in ovarian cancer has been limited by molecular heterogeneity. Although gene expression datasets are available, most of them lack appropriate pair-matched controls to define the alterations that result in the transformation of normal ovarian cells to cancerous cells. Methods: We used microarray to compare the gene expression of treatment-naïve ovarian cancer tissue samples to pair-matched normal adjacent ovarian tissue from 24 patients. Ingenuity Pathway Analysis (IPA) was used to identify target pathways for further analysis. Integrin-linked kinase (ILK) expression in SKOV3 and OV90 cells was determined using Western blot. ILK was knocked down using CRISPR/Cas9 constructs. Subcutaneous xenograft study to determine the effect of ILK knockdown on tumor growth was performed in NOD SCID gamma mice. Results: Significant upregulation of the ILK pathway was identified in 22 of the 24 cancer specimens, identifying it as a potential player that could contribute to the transformation of normal ovarian cells to cancerous cells. Knockdown of ILK in SKOV3 cells resulted in decreased cell proliferation and tumor growth, and inhibition of downstream kinase, AKT (protein kinase B). These results were further validated using an ILK-1 chemical inhibitor, compound 22. Conclusion: Our initial findings validate ILK as a potential therapeutic target for molecular inhibition in ovarian cancer, which warrants further investigation.

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“…Enhanced expression of eS6 (S6) strongly increases the cell migration ability, upregulating MMP2 expression, while knockdown of eS6 reduces cell invasive capacity downregulating MMP9 and MMP2 expression [ 86 ]. The oncogenic and pro-metastatic role of eS6 has been also shown in esophageal squamous cell carcinoma cells as well as in ovarian cancer cells [ 87 , 88 ].…”

Section: Role Of Ribosome Biogenesis In Neoplastic Transformationmentioning

confidence: 99%

“…In particular, eS6 has been proposed as a therapeutic target for patients with ovarian cancer. Knockdown of eS6 by LV-small hairpin RNA (shRNA) remarkably inhibits the migration and invasion ability of ovarian cancer cells and induces G0/G1 phase arrest [ 88 ].…”

Section: Rps As Molecular Target In Cancer Treatmentmentioning

confidence: 99%

Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins

Pecoraro

Pagano

Russo

et al. 2021

IJMS

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Cytosolic ribosomes (cytoribosomes) are macromolecular ribonucleoprotein complexes that are assembled from ribosomal RNA and ribosomal proteins, which are essential for protein biosynthesis. Mitochondrial ribosomes (mitoribosomes) perform translation of the proteins essential for the oxidative phosphorylation system. The biogenesis of cytoribosomes and mitoribosomes includes ribosomal RNA processing, modification and binding to ribosomal proteins and is assisted by numerous biogenesis factors. This is a major energy-consuming process in the cell and, therefore, is highly coordinated and sensitive to several cellular stressors. In mitochondria, the regulation of mitoribosome biogenesis is essential for cellular respiration, a process linked to cell growth and proliferation. This review briefly overviews the key stages of cytosolic and mitochondrial ribosome biogenesis; summarizes the main steps of ribosome biogenesis alterations occurring during tumorigenesis, highlighting the changes in the expression level of cytosolic ribosomal proteins (CRPs) and mitochondrial ribosomal proteins (MRPs) in different types of tumors; focuses on the currently available information regarding the extra-ribosomal functions of CRPs and MRPs correlated to cancer; and discusses the role of CRPs and MRPs as biomarkers and/or molecular targets in cancer treatment.

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Knockdown of ribosomal protein S6 suppresses proliferation, migration, and invasion in epithelial ovarian cancer

Cited by 21 publications

References 30 publications

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

Integrin-Linked Kinase Is a Novel Therapeutic Target in Ovarian Cancer

Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins

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