SP3 is associated with migration, invasion, and Akt/PKB signalling in MDA‐MB‐231 breast cancer cells

Mansour, Mohammed

doi:10.1002/jbt.22657

Cited by 9 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several TFs also gained expression in older LEPs, including: SP3 and ZNF503 ( Figure 3—figure supplement 1Bvi-vii ). SP3 silencing inhibits Akt signaling and breast cancer cell migration and invasion (Mansour, 2020). ZNF503 inhibits GATA3 expression, a key regulator of mammary LEP differentiation, and down regulation is associated with aggressive breast cancers (Kouros-Mehr et al, 2006; Shahi et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility

Sayaman

Miyano

Senapati

et al. 2022

Preprint

View full text Add to dashboard Cite

Effects from aging in any single cell are unpredictable, whereas aging phenotypes at the organ and tissue levels tend to appear as stereotypical changes. The mammary epithelium is a bilayer of two major phenotypically and functionally distinct cell lineages, the luminal epithelial and myoepithelial cells. We have shown that mammary epithelia exhibit substantial stereotypical changes with age which merits attention as they are putative breast cancer cells of origin. We hypothesize that effects from aging that impinge upon maintenance of lineage fidelity increases susceptibility to cancer initiation. From transcriptomic analyses of luminal and myoepithelial lineages from reduction mammoplasties, we identified two models of age-dependent changes in gene expression -- directional changes and increased variance -- that contributed to genome-wide loss of lineage fidelity. Age-dependent variant responses were common to both lineages, whereas directional changes were almost exclusively detected in luminal epithelia and implicated downregulation of chromatin and genome organizers such as SATB1. Epithelial expression of gap junction protein GJB6 increased with age, and modulation of GJB6 expression in heterochronous co-cultures revealed that it provided a communication conduit from myoepithelial cells that drove directional change in luminal cells. Age-dependent luminal transcriptomes comprised a prominent signal detectable in bulk tissue during aging and transition into frank cancers. A luminal-specific aging biomarker machine learning classifier distinguished normal tissue from breast cancers and was predictive of PAM50 breast cancer subtypes. The variability in expression of age-dependent genes across individuals may influence differential susceptibility to breast cancer initiation in a subtype-specific manner. We speculate that luminal epithelia are the ultimate site of integration of the variant responses to aging in their surrounding tissue and that their emergent aging phenotype both endows cells with the ability to become cancer cells of origin and embodies a biosensor that presages cancer susceptibility.

show abstract

Section: Resultsmentioning

confidence: 99%

Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility

Sayaman

Miyano

Senapati

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…ZNF503 inhibits GATA3 expression, a key regulator of mammary LEP differentiation, and down regulation is associated with aggressive breast cancers [Shahi et al, 2017, Kouros-Mehr et al, 2006. And SP3 silencing inhibits Akt signaling and breast cancer cell migration and invasion [Mansour, 2020]. Aging caused significant changes in TFs in the LEP lineage that are known to have roles in breast cancer.…”

Section: These Molecular Changes Recapitulated Previous Phenotypic Obmentioning

confidence: 99%

Epigenetic changes with age primes mammary luminal epithelia for cancer initiation

Sayaman

Miyano

Senapati

et al. 2021

Preprint

View full text Add to dashboard Cite

Aging causes molecular changes that manifest as stereotypical phenotypes yet aging-associated diseases progress only in certain individuals. At lineage-specific resolution, we show how stereotyped and variant responses are integrated in mammary epithelia. Age-dependent directional changes in gene expression and DNA methylation (DNAm) occurred almost exclusively in luminal cells and implicated genome organizers SATB1 and CTCF. DNAm changes were robust indicators of aging luminal cells, and were either directly (anti-)correlated with expression changes or served as priming events for subsequent dysregulation, such as demethylation of ESR1-binding regions in DNAm-regulatory CXXC5 in older luminal cells and luminal-subtype cancers. Variance-driven changes in the transcriptome of both luminal and myoepithelial lineages further contributed to age-dependent loss of lineage fidelity. The pathways affected by transcriptomic and DNAm changes during aging are commonly linked with breast cancer, and together with the differential variability found across individuals, influence aging-associated cancer susceptibility in a subtype-specific manner.

show abstract

“…TP53 and CD59 were most highly expressed in the CellScore low group (Supplementary Figure 4F-4I). SP3 was a member of SP-family and was an oncogene that played a pivotal role in cell proliferation and metastasis of various tumors [42][43][44][45][46]. ATF2 was also an oncogene that is associated with the progression and resistance to anti-tumor therapy, including HNSCC [47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

A novel oxidative stress-related gene signature as an indicator of prognosis and immunotherapy responses in HNSCC

Li,

Zheng,

Liu

et al. 2023

Aging

View full text Add to dashboard Cite

Purpose: To identify molecular subtypes of oxidative stress-related genes in head and neck squamous cell carcinoma (HNSCC) and to construct a scoring model of oxidative stress-related genes. Methods: R language based scRNA-seq and bulk RNA-seq analyses were used to identify molecular isoforms of oxidative stress-related genes in HNSCC. An oxidative stress-related gene scoring (OSRS) model was constructed, which were verified through online data and immunohistochemical staining of clinical samples. Results: Using TCGA-HNSCC datasets, nine predictive genes for overall patient survival, rarely reported in previous similar studies, were screened. AREG and CES1 were identified as prognostic risk factors. CSTA, FDCSP, JCHAIN, IFFO2, PGLYRP4, SPOCK2 and SPINK6 were identified as prognostic factors. Collectively, all genes formed a prognostic risk signature model for oxidative stress in HNSCC, which were validated in GSE41613, GSE103322 and PRJEB23709 datasets. Immunohistochemical staining of SPINK6 in nasopharyngeal cancer samples validated the gene panel. Subsequent analysis indicated that subgroups of the oxidative stress prognostic signature played important roles during cellular communication, the immune microenvironment, the differential activation of transcription factors, oxidative stress and immunotherapeutic responses. Conclusions: The risk model might predict HNSCC prognosis and immunotherapeutic responses.

show abstract

SP3 is associated with migration, invasion, and Akt/PKB signalling in MDA‐MB‐231 breast cancer cells

Cited by 9 publications

References 34 publications

Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility

Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility

Epigenetic changes with age primes mammary luminal epithelia for cancer initiation

A novel oxidative stress-related gene signature as an indicator of prognosis and immunotherapy responses in HNSCC

Contact Info

Product

Resources

About