Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1

Bagati, Archis; Bianchi‐Smiraglia, Anna; Moparthy, Sudha; Kolesnikova, Kateryna; Fink, Emily E.; Lipchick, Brittany C.; Kolesnikova, Masha; Jowdy, Peter; Polechetti, Anthony; Mahpour, Amin; Ross, Jason T.; Wawrzyniak, Joseph A.; Yun, Dong Hyun; Paragh, György; Kozlova, N. I.; Berman, A. E.; Wang, Jianmin; Liu, Song; Nemeth, Michael J.; Nikiforov, Mikhail A.

doi:10.1016/j.celrep.2017.08.057

Cited by 23 publications

(29 citation statements)

References 46 publications

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“…In contrast, we observed residual pathway activation by FOXB2 in β-catenin–deficient cells. Some FOX proteins, e.g., FOXQ1 and FOXM1, control β-catenin activity via direct association (20, 22). However, FOXB2 did not bind β-catenin or colocalize with nuclear β-catenin ( SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

Wnt activator FOXB2 drives the neuroendocrine differentiation of prostate cancer

Moparthi

Pizzolato

Koch

2019

Proc. Natl. Acad. Sci. U.S.A.

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The Wnt signaling pathway is of paramount importance for development and disease. However, the tissue-specific regulation of Wnt pathway activity remains incompletely understood. Here we identify FOXB2, an uncharacterized forkhead box family transcription factor, as a potent activator of Wnt signaling in normal and cancer cells. Mechanistically, FOXB2 induces multiple Wnt ligands, including WNT7B, which increases TCF/LEF-dependent transcription without activating Wnt coreceptor LRP6 or β-catenin. Proximity ligation and functional complementation assays identified several transcription regulators, including YY1, JUN, and DDX5, as cofactors required for FOXB2-dependent pathway activation. Although FOXB2 expression is limited in adults, it is induced in select cancers, particularly advanced prostate cancer. RNA-seq data analysis suggests that FOXB2/WNT7B expression in prostate cancer is associated with a transcriptional program that favors neuronal differentiation and decreases recurrence-free survival. Consistently, FOXB2 controls Wnt signaling and neuroendocrine differentiation of prostate cancer cell lines. Our results suggest that FOXB2 is a tissue-specific Wnt activator that promotes the malignant transformation of prostate cancer.

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Section: Resultsmentioning

confidence: 99%

Wnt activator FOXB2 drives the neuroendocrine differentiation of prostate cancer

Moparthi

Pizzolato

Koch

2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Among other miR-204-5p target genes, CDH2 and FOXC1 should also be under consideration. CDH2 is a gene that codes N-cadherin, which is broadly expressed in melanoma cells, serving as a promotor of melanoma cell invasion and metastasis via triggering several signaling cascades and transcription factors ( 39 ). N-cadherin-overexpressing melanoma cells lose contacts with neighboring keratinocytes and demonstrate increased adhesion and motility features ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑204‑5p and miR‑3065‑5p exert antitumor effects on melanoma cells

et al. 2018

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MicroRNA (miR)-204-5p was previously identified to be downregulated in melanoma compared with melanocytic nevi. This observation prompted a functional study on miR-204-5p and the newly-identified miR-3065-5p, two miRNAs suggested to be tumor-suppressive oncomiRs. Application of miR-204-5p mimics or inhibitors resulted in a decrease or increase, respectively, in melanoma cell proliferation and colony formation. miR-204-5p mimics hindered invasion, whereas miR-204-5p inhibitors stimulated cancer cell migration. Modulation of miR-3065-5p led to a decrease in melanoma cell proliferation, altered cell cycle distribution and increased expression levels of its target genes HIPK1 and ITGA1, possibly due to functional modifications identified in these cells. miR-204-5p and miR-3065-5p demonstrated antitumor capacities that may need to be taken into account in the development of melanoma treatment approaches.

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“…However, albeit FOXQ1 is in general considered as an oncoprotein, a recent study demonstrated that FOXQ1 can also act as a tumor suppressor in melanomas (106). It is possible that the same holds true for prostate cancer, as it was found that FOXQ1 was downregulated in prostate tumors, and this downregulation was even accentuated upon metastasis (Fig.…”

Section: Discussionmentioning

confidence: 93%

Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer

Song

Freeman

et al. 2020

Int J Oncol

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ETS variant 1 (ETV1) is an oncogenic transcription factor. However, its role in colorectal cancer has remained understudied. The present study demonstrated that ETV1 downregulation led to reduced HCT116 colorectal cancer cell growth and clonogenic activity. Furthermore, the ETV1 mRNA levels were enhanced in colorectal tumors and were associated with disease severity. In addition, ETV1 directly bound to Jumonji C domain-containing (JMJD) 1A, a histone demethylase known to promote colon cancer. ETV1 and JMJD1A, but not a catalytically inactive mutant thereof, cooperated in inducing the matrix metalloproteinase (MMP)1 gene promoter that was similar to the cooperation between ETV1 and another histone demethylase, JMJD2A. RNA-sequencing revealed multiple potential ETV1 target genes in HCT116 cells, including the FOXQ1 and TBX6 transcription factor genes. Moreover, JMJD1A co-regulated FOXQ1 and other ETV1 target genes, but not TBX6, whereas JMJD2A downregulation had no impact on FOXQ1 as well as TBX6 transcription. Accordingly, the FOXQ1 gene promoter was stimulated by ETV1 and JMJD1A in a cooperative manner, and both ETV1 and JMJD1A bound to the FOXQ1 promoter. Notably, the overexpression of FOXQ1 partially reversed the growth inhibitory effects of ETV1 ablation on HCT116 cells, whereas TBX6 impaired HCT116 cell growth and may thereby dampen the oncogenic activity of ETV1. The latter also revealed for the first time, to the best of our knowledge, a potential tumor suppressive function of TBX6. Taken together, the present study uncovered a ETV1/JMJD1A-FOXQ1 axis that may drive colorectal tumorigenesis.

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Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1

Cited by 23 publications

References 46 publications

Wnt activator FOXB2 drives the neuroendocrine differentiation of prostate cancer

Wnt activator FOXB2 drives the neuroendocrine differentiation of prostate cancer

miR‑204‑5p and miR‑3065‑5p exert antitumor effects on melanoma cells

Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer

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