NFIB promotes cell survival by directly suppressing p21 transcription in <i>TP53</i>‐mutated triple‐negative breast cancer

Liu, Rong‐Zong; Vo, The M; Jain, Saket; Choi, Wonshik; Garcia, Elizabeth; Monckton, Elizabeth A.; Mackey, John R.; Godbout, Roseline

doi:10.1002/path.5182

Cited by 38 publications

(36 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Omomyc has been instrumental in demonstrating this therapeutic opportunity, first as a transgene [20] and more recently as a therapeutic polypeptide, [40] while also demonstrating the complete safety of the approach for normal tissues. [42] The present study proves that P31 is packable as IBs while keeping relevant antitumoral functionalities. P31, so far neglected regarding its potential uses as a therapeutic agent, has been directly linked to the control of p21 expression and pro-apoptotic activity, especially in triple negative breast cancers (TNBC).…”

Section: Resultssupporting

confidence: 67%

Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies

Pesarrodona

Jauset²,

Díaz‐Riascos

et al. 2019

Advanced Science

View full text Add to dashboard Cite

Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44‐targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.

show abstract

Section: Resultssupporting

confidence: 67%

Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies

Pesarrodona

Jauset²,

Díaz‐Riascos

et al. 2019

Advanced Science

View full text Add to dashboard Cite

show abstract

“…Recently, accumulating evidence indicated the NFI transcription factors have both oncogenic and tumor-suppressive potential, depending on the context. For example, NFIB, the most well studied NFI transcription factor, might be oncogenic in SCLC (Dooley et al, 2011), melanoma, and breast cancer (Fane et al, 2017;Liu et al, 2019), but likely functions as a tumor suppressor in NSCLC (Becker-Santos et al, 2016), osteosarcoma (Mirabello et al, 2015), glioma and glioblastoma (Stringer et al, 2016;Suzuki et al, 2015). Similarly, NFIB and NFIC could function in an opposing role.…”

Section: Discussionmentioning

confidence: 99%

“…The breast cancer cell line, MCF7, treated with NFIC siRNA, enhanced EMT, motility, migration and invasion (Lee, Lee & Park, 2015). Conversely, depletion of NFIB in p53-mutated triple-negative breast cancer cell lines MDA-MB-435, HCC1806 and BT-20, promoted cell death, cell cycle arrest, and enhanced sensitivity to docetaxel, a first-line chemotherapeutic drug used in breast cancer treatment (Liu et al, 2019). Furthermore, NFIA inhibited cell death and enhanced cell survival, proliferation, and migration in GBM by negatively regulating p53, p21 and PAI1 (Kang et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Transcription levels and prognostic significance of the NFI family members in human cancers

Sun

Tan

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background The nuclear factor I (NFI) is a family of transcription factors consisting of four distinct but closely related genes, NFIA, NFIB, NFIC and NFIX, which are important in the development of various tissues and organs in mammals. Recent study results have shown that NFI family may play a critical role in the progression of various human tumors and have been identified as key tumor suppressors and oncogenes for many cancers. However, the expression levels and distinctive prognostic values of the NFI family remain poorly explored in most cancers. Materials and Methods In the present study, the differences in mRNA expression of the NFI family in various cancers were investigated using the Oncomine and TCGA databases, and the mRNA expression, genetic alteration and DNA methylation of the NFI family members in various cancers were examined using cBioPortal for Cancer Genomics. In addition, the prognostic significance of the NFI family was assessed in multiple cancers using the Kaplan–Meier plotter (KM plotter) and SurvExpress databases. Results The mRNA expression levels in the NFI family were significantly downregulated in most cancers compared with normal tissues and DNA hypermethylation might downregulate the NFI family expression. Although NFIX expression was not downregulated in kidney, colorectal and prostate cancers. Furthermore, NFIB expression was upregulated in gastric cancer. Further survival analyses based on the KM plotter and SurvExpress databases showed dysregulations of the NFI genes were significantly correlated with survival outcomes in breast, lung, and head and neck cancers. Decreased expression levels of NFIA, NFIB and NFIC were associated with poor overall survival (OS) in head and neck cancer. Low mRNA expression of NFIA and NFIB was significantly associated with OS and first progression in lung adenocarcinoma, but not in lung squamous cell carcinoma. In addition, potential correlations between NFI family members and survival outcomes were also observed in liver, esophageal, kidney and cervical cancer. Conclusion The results from the present study indicated certain members of the NFI family could be promising therapeutic targets and novel prognostic biomarkers for human cancers.

show abstract

“…On the other hand, culturing hCECs in the presence of i3T3 had a much greater impact than iHFL on both the expression and DNA binding of NFI, a result that can also be explained essentially by an i3T3-dependent increase in the expression of the NFIB isoform ( Figure 4A; also see Figure 9). This increase in NFIB expression is puzzling in that NFIB was recently identified as a new oncogene in small cell lung cancer [36][37][38] and most particularly in triple negative breast cancer (TNBC), where it contributes to cell proliferation/survival through a direct suppression of p21 transcription [39]. NFIB has been recognized as a TF that can either promote or suppress human cancers in a cancer-type dependent manner [40,41].…”

Section: Discussionmentioning

confidence: 99%

Irradiated Human Fibroblasts as a Substitute Feeder Layer to Irradiated Mouse 3T3 for the Culture of Human Corneal Epithelial Cells: Impact on the Stability of the Transcription Factors Sp1 and NFI

Le‐Bel

Ghio

Guérin

et al. 2019

IJMS

View full text Add to dashboard Cite

Because of the worldwide shortage of graftable corneas, alternatives to restore visual impairments, such as the production of a functional human cornea by tissue engineering, have emerged. Self-renewal of the corneal epithelium through the maintenance of a sub-population of corneal stem cells is required to maintain the functionality of such a reconstructed cornea. We previously reported an association between stem cell differentiation and the level to which they express the transcription factors Sp1 and NFI. In this study, we investigated the impact of replacing irradiated 3T3 (i3T3) murine fibroblast feeder cells by irradiated human corneal fibroblasts (iHFL) on the expression of Sp1 and NFI and evaluated their contribution to the proliferative properties of human corneal epithelial cells (hCECs) in both monolayer cultures and human tissue engineered corneas (hTECs). hCECs co-cultured with iHFL could be maintained for up to two more passages than when they were grown with i3T3. Western Blot and electrophoretic mobility shift assays (EMSAs) revealed no significant difference in the feeder-layer dependent increase in Sp1 at both the protein and DNA binding level, respectively, between HCECs grown with either i3T3 or iHFL. On the other hand, a significant increase in the expression and DNA binding of NFI was observed at each subsequent passage when hCECs were co-cultured along with i3T3. These changes were found to result from an increased expression of the NFIA and NFIB isoforms in hCECs grown with i3T3. Exposure of hCECs to cycloheximide revealed an increased stability of NFIB that likely resulted from post-translational glycosylation of this protein when these cells were co-cultured with i3T3. In addition, iHFL were as efficient as i3T3 at preserving corneal, slow-cycling, epithelial stem cells in the basal epithelium of the reconstructed hTECs. Furthermore, we observed an increased expression of genes whose encoded products promote hCECs differentiation along several passages in hCECs co-cultured with either type of feeder layer. Therefore, the iHFL feeder layer appears to be the most effective at maintaining the proliferative properties of hCECs in culture most likely by preserving high levels of Sp1 and low levels of NFIB, which is known for its gene repressor and cell differentiation properties.

show abstract

NFIB promotes cell survival by directly suppressing p21 transcription in TP53‐mutated triple‐negative breast cancer

Cited by 38 publications

References 45 publications

Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies

Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies

Transcription levels and prognostic significance of the NFI family members in human cancers

Irradiated Human Fibroblasts as a Substitute Feeder Layer to Irradiated Mouse 3T3 for the Culture of Human Corneal Epithelial Cells: Impact on the Stability of the Transcription Factors Sp1 and NFI

Contact Info

Product

Resources

About