CCAAT enhancer binding protein α suppresses proliferation, metastasis, and epithelial-mesenchymal transition of ovarian cancer cells via suppressing the Wnt/β-catenin signaling

Zhang, Limei; Li, Mo; Tian, Chenchen; Wang, Tongtong; Mi, Shu-Fang

doi:10.4149/neo_2021_210103n2

Cited by 8 publications

(2 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The five downregulated genes were CEBPA, DIRAS3, COL2A1, ZNF750, and CT45A5. Low expression of the CEBPA transcription factor is associated with poorer overall survival and growth and progression phenotypes in ovarian cancer cell lines, and has been shown to repress WNT signaling 55 . DIRAS3 is a member of the Ras super-family that is an imprinted tumor suppressor gene.…”

Section: Discussionmentioning

confidence: 99%

Cell-intrinsic platinum response and associated genetic and gene expression signatures in ovarian cancer cell lines and isogenic models

Adams,

Wendt,

Wood

et al. 2024

Preprint

View full text Add to dashboard Cite

Ovarian cancers are still largely treated with platinum-based chemotherapy as the standard of care, yet few biomarkers of clinical response have had an impact on clinical decision making as of yet. Two particular challenges faced in mechanistically deciphering platinum responsiveness in ovarian cancer have been the suitability of cell line models for ovarian cancer subtypes and the availability of information on comparatively how sensitive ovarian cancer cell lines are to platinum. We performed one of the most comprehensive profiles to date on 36 ovarian cancer cell lines across over seven subtypes and integrated drug response and multiomic data to improve on our understanding of the best cell line models for platinum responsiveness in ovarian cancer. RNA-seq analysis of the 36 cell lines in a single batch experiment largely conforms with the currently accepted subtyping of ovarian cancers, further supporting other studies that have reclassified cell lines and demonstrate that commonly used cell lines are poor models of high-grade serous ovarian carcinoma. We performed drug dose response assays in the 32 of these cell lines for cisplatin and carboplatin, providing a quantitative database of IC50s for these drugs. Our results demonstrate that cell lines largely fall either well above or below the equivalent dose of the clinical maximally achievable dose (Cmax) of each compound, allowing designation of cell lines as sensitive or resistant. We performed differential expression analysis for high-grade serous ovarian carcinoma cell lines to identify gene expression correlating with platinum-response. Further, we generated two platinum-resistant derivatives each for OVCAR3 and OVCAR4, as well as leveraged clinically-resistant PEO1/PEO4/PEO6 and PEA1/PEA2 isogenic models to perform differential expression analysis for seven total isogenic pairs of platinum resistant cell lines. While gene expression changes overall were heterogeneous and vast, common themes were innate immunity/STAT activation, epithelial to mesenchymal transition and stemness, and platinum influx/efflux regulators. In addition to gene expression analyses, we performed copy number signature analysis and orthogonal measures of homologous recombination deficiency (HRD) scar scores and copy number burden, which is the first report to our knowledge applying field-standard copy number signatures to ovarian cancer cell lines. We also examined markers and functional readouts of stemness that revealed that cell lines are poor models for examination of stemness contributions to platinum resistance, likely pointing to the fact that this is a transient state. Overall this study serves as a resource to determine the best cell lines to utilize for ovarian cancer research on certain subtypes and platinum response studies, as well as sparks new hypotheses for future study in ovarian cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Cell-intrinsic platinum response and associated genetic and gene expression signatures in ovarian cancer cell lines and isogenic models

Adams,

Wendt,

Wood

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…EMT is mainly responsible for cancer cell migration and invasion ( Yilmaz & Christofori, 2009 ). In cancer, the Wnt/β-catenin signaling pathway is a classic route that activates EMT ( Bugter, Fenderico & Maurice, 2021 ; Zhang et al, 2021 ; Zhang & Wang, 2020 ). Furthermore, β-catenin may control the EMT-related transcription factors expression as the primary downstream effector of Wnt/β-catenin signaling ( Gonzalez & Medici, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

CTHRC1 promotes anaplastic thyroid cancer progression by upregulating the proliferation, migration, and invasion of tumor cells

Chen

Jia

Zhao

et al. 2023

PeerJ

View full text Add to dashboard Cite

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive tumor with a high mortality rate and poor prognosis. However, the pathogenesis of ATC is complex and poorly understood, and the effective treatment options are limited. Analysis of data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases showed that collagen triple helix repeat containing-1 (CTHRC1) was specifically upregulated in ATC tissues and was negatively correlated with overall survival (OS) in thyroid carcinoma patients. In vitro knockdown of CTHRC1 dramatically decreased the proliferation, migration, and invasion abilities of ATC cells, and in vivo studies in BALB/c nude mice confirmed that CTHRC1 knockdown significantly inhibited tumor growth. Mechanistically, CTHRC1 knockdown was found to suppress the Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT) at the protein level. These findings suggest that CTHRC1 promotes the progression of ATC via upregulating tumor cell proliferation, migration, and invasion, which may be achieved by activating the Wnt/β-catenin pathway and EMT.

show abstract

Wnt/β-catenin-driven EMT regulation in human cancers

Xue,

Yang,

Chen

et al. 2024

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Metastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial–mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/β-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3β that destructs β-catenin, while ligand–receptor interaction impairs GSK-3β function to increase β-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/β-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance β-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/β-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/β-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression. Graphical abstract

show abstract

CCAAT enhancer binding protein α suppresses proliferation, metastasis, and epithelial-mesenchymal transition of ovarian cancer cells via suppressing the Wnt/β-catenin signaling

Cited by 8 publications

References 25 publications

Cell-intrinsic platinum response and associated genetic and gene expression signatures in ovarian cancer cell lines and isogenic models

Cell-intrinsic platinum response and associated genetic and gene expression signatures in ovarian cancer cell lines and isogenic models

CTHRC1 promotes anaplastic thyroid cancer progression by upregulating the proliferation, migration, and invasion of tumor cells

Wnt/β-catenin-driven EMT regulation in human cancers

Contact Info

Product

Resources

About