<i>PELP1</i> inhibition by <scp>SMIP34</scp> reduces endometrial cancer progression via attenuation of ribosomal biogenesis

Yang, Xue; Liu, Zexuan; Tang, Weiwei; Pratap, Uday P.; Collier, Alexia B.; Altwegg, Kristin A.; Gopalam, Rahul; Li, Xiaonan; Yuan, Yaxia; Zhou, Daohong; Lai, Zhao; Chen, Yidong; Sareddy, Gangadhara R.; Valente, Philip T.; Kost, Edward R.; Viswanadhapalli, Suryavathi; Vadlamudi, Ratna K.

doi:10.1002/1878-0261.13539

Cited by 4 publications

(2 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This cascades into the downregulation of key Rix1 components—WDR18, TEX10, LAS1L, and SENP3—resulting in a subsequent reduction in rRNA synthesis. ( 284 ). Early studies have showcased the efficacy of SMIP34 in reducing the progression of endometrial cancer and ER-positive breast cancer, highlighting the potential of exploring rRNA processing factors as valuable therapeutic targets ( 284–286 ).…”

Section: Targeting Ribosome Biogenesis For Cancer Therapeuticsmentioning

confidence: 99%

See 1 more Smart Citation

The impact of ribosome biogenesis in cancer: from proliferation to metastasis

Hwang,

Denicourt

2024

NAR Cancer

View full text Add to dashboard Cite

The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating the adaptation to altered translational demands essential for various aspects of tumor progression. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting dynamic regulation orchestrated by key oncogenic signaling pathways. Recent studies reveal the multifaceted roles of ribosomes, extending beyond protein factories to include regulatory functions in mRNA translation. Dysregulated ribosome biogenesis not only hampers precise control of global protein production and proliferation but also influences processes such as the maintenance of stem cell-like properties and epithelial-mesenchymal transition, contributing to cancer progression. Interference with ribosome biogenesis, notably through RNA Pol I inhibition, elicits a stress response marked by nucleolar integrity loss, and subsequent G1-cell cycle arrest or cell death. These findings suggest that cancer cells may rely on heightened RNA Pol I transcription, rendering ribosomal RNA synthesis a potential therapeutic vulnerability. The review further explores targeting ribosome biogenesis vulnerabilities as a promising strategy to disrupt global ribosome production, presenting therapeutic opportunities for cancer treatment.

show abstract

Section: Targeting Ribosome Biogenesis For Cancer Therapeuticsmentioning

confidence: 99%

“…( 284 ). Early studies have showcased the efficacy of SMIP34 in reducing the progression of endometrial cancer and ER-positive breast cancer, highlighting the potential of exploring rRNA processing factors as valuable therapeutic targets ( 284–286 ).…”

Section: Targeting Ribosome Biogenesis For Cancer Therapeuticsmentioning

confidence: 99%

The impact of ribosome biogenesis in cancer: from proliferation to metastasis

Hwang,

Denicourt

2024

NAR Cancer

View full text Add to dashboard Cite

show abstract

PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma

Nassar,

Yang,

Baker

et al. 2024

Cancer Research Communications

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States, with a median survival period of approximately 10 months. There is an urgent need for the development of effective targeted therapies for the treatment of HCC. Proline-, glutamic acid–, and leucine-rich protein 1 (PELP1) signaling is implicated in the progression of many cancers, although its specific contribution to the progression of HCC is not yet well understood. Analysis of The Cancer Genome Atlas HCC gene expression data sets and IHC analysis of HCC tissue microarray revealed that HCC tumors had elevated expression of PELP1 compared with normal tissues, and high expression of PELP1 is associated with unfavorable survival outcomes. Suppression of PELP1 expression using short hairpin RNA significantly reduced the cell viability, clonogenicity, and invasion of HCC cells. Importantly, SMIP34, a first-in-class small-molecule inhibitor targeting PELP1, effectively decreased the cell viability, clonogenic survival, and invasiveness of HCC cells. Gene expression analysis using RNA sequencing revealed that PELP1 knockdown cells exhibited a decrease in c-Myc, E2F, and other oncogenic pathways related to HCC. Mechanistic studies showed that SMIP34 treatment impaired the Rix complex, a critical component of ribosomal biogenesis, in HCC cells. Furthermore, the knockdown or pharmacologic inhibition of PELP1 significantly decelerated the HCC tumor growth in xenograft models. In summary, our study findings indicate that PELP1 could serve as a promising target for therapeutic intervention in HCC. Significance: HCC is one of the leading causes of cancer fatalities in the United States. Effective targeted therapeutics for HCC are urgently needed. In this study, we show that PELP1 proto-oncogene is crucial to HCC progression and that PELP1 inhibition reduced HCC cell proliferation in vitro and in vivo. Our results imply that PELP1-targeted drugs like SMIP34 may be useful as new therapeutic agents for HCC treatment.

show abstract

The use of organoids in creating immune microenvironments and treating gynecological tumors

Zhou,

Liao,

Han

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Owing to patient-derived tumor tissues and cells, significant advances have been made in personalized cancer treatment and precision medicine, with cancer stem cell-derived three-dimensional tumor organoids serving as crucial in vitro models that accurately replicate the structural, phenotypic, and genetic characteristics of tumors. However, despite their extensive use in drug testing, genome editing, and transplantation for facilitating personalized treatment approaches in clinical practice, the inadequate capacity of these organoids to effectively model immune cells and stromal components within the tumor microenvironment limits their potential. Additionally, effective clinical immunotherapy has led the tumor immune microenvironment to garner considerable attention, increasing the demand for simulating patient-specific tumor–immune interactions. Consequently, co-culture techniques integrating tumor organoids with immune cells and tumor microenvironment constituents have been developed to expand the possibilities for personalized drug response investigations, with recent advancements enhancing the understanding of the strengths, limitations, and applicability of the co-culture approach. Herein, the recent advancements in the field of tumor organoids have been comprehensively reviewed, specifically highlighting the tumor organoid co-culture-related developments with various immune cell models and their implications for clinical research. Furthermore, this review delineates the current state of research and application of organoid models regarding the therapeutic approaches and related challenges for gynecological tumors. This study may provide a theoretical basis for further research on the use of patient-derived organoids in tumor immunity, drug development, and precision medicine.

show abstract

PELP1 inhibition by SMIP34 reduces endometrial cancer progression via attenuation of ribosomal biogenesis

Cited by 4 publications

References 46 publications

The impact of ribosome biogenesis in cancer: from proliferation to metastasis

The impact of ribosome biogenesis in cancer: from proliferation to metastasis

PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma

The use of organoids in creating immune microenvironments and treating gynecological tumors

Contact Info

Product

Resources

About