GON4L Drives Cancer Growth through a YY1–Androgen Receptor–CD24 Axis

Agarwal, Neeraj; Dancik, Garrett M.; Goodspeed, Andrew; Costello, James C.; Owens, Charles; Duex, Jason E.; Theodorescu, Dan

doi:10.1158/0008-5472.can-16-1099

Cited by 39 publications

(27 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD24 is a glycosylphosphatidylinositol-anchored membrane protein reported to be overexpressed in many tumor types, including colorectal cancer, 13 ovarian cancer, 7 bladder cancer, 14 prostate cancer, 5,11 lung cancer, 12 and breast cancer. 9 CD24 plays important roles in tumorigenesis, [35][36][37] progression [38][39][40] and drug resistance. 18,41 CD24 is considered to be a negative cancer stem cell marker, specifically in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Li¹,

Chen²,

Ge³

et al. 2019

OTT

View full text Add to dashboard Cite

Introduction: CD24 is known as a heavily glycosylated cell surface molecule that is highly expressed in a wide variety of human malignancies. Previous studies have shown that CD24 plays an important role in self-renewal, proliferation, migration, invasion and drug resistance of hepatocellular carcinoma (HCC). However, little is known about the expression and function of CD24 isoform a (CD24A) and CD24 isoform b (CD24B) in HCC. Materials and methods: Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were performed to detect CD24 and EGR1 expression in HCC cells and tissue. The function of CD24 in cell proliferation was verified with MTT assays, colony formation assays and tumor xenograft models. Wound healing assays and invasion assays were performed to clarify the function of CD24 in the regulation of cell migration and invasion in HCC. A dual luciferase reporter assay and chromatin immunoprecipitation assay were used to analyze the regulation mechanism of CD24A. Results: CD24A but not CD24B, which was barely detected by qPCR and Western blotting, is significantly upregulated in HCC tissue. Both CD24A and CD24B contribute to HCC cell proliferation, migration and invasion, but CD24A is more effective than CD24B. EGR1 downregulates CD24A and exerts transcription-promoting activity on the CD24A promoter. Furthermore, EGR1 represses HCC cell proliferation via downregulation of CD24A. Conclusion: CD24A is the predominant CD24 isoform in HCC and plays a major role in cell proliferation, migration, and invasion. EGR1 can exert its antitumor effect through transcriptional downregulation of CD24A in HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Li¹,

Chen²,

Ge³

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…KLF4 was reported to be downregulated in UC and act as a metastasis suppressor inhibiting EMT [85] . Androgen receptor (AR) was reported to promote UC metastasis by affecting CD24 [86] , [87] , [88] . Several investigators reported that infiltrating neutrophils [89] and B lymphocytes [90] modulated AR transactivation leading to elevated MMPs expression and cell invasion.…”

Section: Metastasis Promoters and Suppressors Of Ucmentioning

confidence: 99%

Understanding the biology of urothelial cancer metastasis

Kobayashi

2016

Asian Journal of Urology

View full text Add to dashboard Cite

Management of unresectable urothelial cancer (UC) has been a clinical challenge for decades. While drug resistance is a key issue, precise understanding of biology of UC metastasis is another challenge for the improvement of treatment outcome of UC patients. Introduction of the cell biology concepts including epithelial-mesenchymal transition (EMT) and cancer stemness seems to explain UC metastasis. Molecular genetics based on gene expression profiling, next generation sequencing, and explosion of non-coding RNA world has opened the door to intrinsic molecular subtyping of UC. Next steps include, based on the recently accumulated understanding, the establishment of novel disease models representing UC metastasis in various experimental platforms, particularly in vivo animal systems. Indeed, novel knowledge molecular genetics has not been fully linked to the modeling of UC metastasis. Further understanding of bladder carcinogenesis is needed particularly with regard to cell of origin related to tumor characteristics including driver gene alterations, pathological differentiations, and metastatic ability. Then we will be able to establish better disease models, which will consequently lead us to further understanding of biology and eventually the development of novel therapeutic strategies for UC metastasis.

show abstract

“…Further, other studies suggested GON4L drives proliferation by human cancer cells (38–40). Given these findings, we explored the possibility that GON4L deficiency due to the Justy mutation affects the expression of genes that control cell-cycle progression and division.…”

Section: Resultsmentioning

confidence: 92%

“…For example, GON4L deficiency in zebrafish embryos blocks erythropoiesis, somite formation, and tail extension, which was correlated with cell cycle arrest and apoptosis (34, 37). Validating a role in cell division, other studies identified GON4L as important for the growth of cultured human cancer cells (38–40). …”

Section: Introductionmentioning

confidence: 99%

Early B Cell Progenitors Deficient for GON4L Fail To Differentiate Due to a Block in Mitotic Cell Division

Barr

Goodfellow

Colgan

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

B cell development in Justy mutant mice is blocked due to a pre-mRNA splicing defect that depletes the protein GON4-like (GON4L) in B cell progenitors. Genetic and biochemical studies have suggested GON4L is a transcriptional regulator that coordinates cell division with differentiation, but its role in B cell development is unknown. To understand the function of GON4L, we characterized B cell differentiation, cell cycle control, and mitotic gene expression in GON4L-deficient B cell progenitors from Justy mice. We found that these cells established key aspects of the transcription factor network that guides B cell development and proliferation and rearranged the immunoglobulin heavy chain gene locus. However, despite intact IL-7 signaling, GON4L-deficient pro-B cell stage precursors failed to undergo a characteristic IL-7-dependent proliferative burst. These cells also failed to upregulate genes required for mitotic division, including those encoding the G1/S cyclin D3 and E2F transcription factors and their targets. Additionally, GON4L-deficient B cell progenitors displayed defects in DNA synthesis and passage through the G1/S transition, contained fragmented DNA and underwent apoptosis. These phenotypes were not suppressed by transgenic expression of pro-survival factors. However, transgenic expression of cyclin D3 or other regulators of the G1/S transition restored pro-B cell development from Justy progenitor cells, suggesting GON4L acts at the beginning of the cell cycle. Together, our findings indicate GON4L is essential for cell cycle progression and division during the early stages of B cell development.

show abstract

GON4L Drives Cancer Growth through a YY1–Androgen Receptor–CD24 Axis

Cited by 39 publications

References 51 publications

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Understanding the biology of urothelial cancer metastasis

Early B Cell Progenitors Deficient for GON4L Fail To Differentiate Due to a Block in Mitotic Cell Division

Contact Info

Product

Resources

About