Vestigial-like 1 (VGLL1): An ancient co-transcriptional activator linking wing, placenta, and tumor development

Sonnemann, Heather M.; Pazdrak, Barbara; Antunes, Dinler Amaral; Roszik, Jason; Lizée, Gregory

doi:10.1016/j.bbcan.2023.188892

Cited by 4 publications

(5 citation statements)

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“…Transcriptomic analyses of normal human tissues have shown that the co-transcriptional activator VGLL1 demonstrates uniquely elevated expression within the placenta ( 4 , 5 , 39 ). VGLL1 is also overexpressed in multiple cancer types, demonstrating predominant expression in basal-like breast and pancreatic cancers with transcription increased by 8- to 60-fold compared to normal breast and pancreatic tissue ( 3 , 4 , 40 ). Emerging evidence has suggested that tumor cells may co-opt attributes of normal placental VGLL1 function to promote invasion, proliferation, and tumor progression ( 3 , 8 , 9 ).…”

Section: Discussionmentioning

confidence: 99%

“…VGLL1 is also overexpressed in multiple cancer types, demonstrating predominant expression in basal-like breast and pancreatic cancers with transcription increased by 8- to 60-fold compared to normal breast and pancreatic tissue ( 3 , 4 , 40 ). Emerging evidence has suggested that tumor cells may co-opt attributes of normal placental VGLL1 function to promote invasion, proliferation, and tumor progression ( 3 , 8 , 9 ). In this study, we demonstrated that modulation of VGLL1 expression has a marked impact on cell invasion and proliferation in multiple cancer cell types, and that it can interact with several known TFs to drive the expression of multiple genes involved in these pathways to promote tumor growth and metastasis ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…Studies over the past decade have begun illuminating the role of mammalian VGLL1 and have focused largely on two broad areas of developmental biology: normal placental development and tumorigenesis. VGLL1 is expressed at a low to negligible level in most normal tissues but demonstrates by far the highest expression in placental trophoblasts ( 3 – 5 ). These cells are highly proliferative and invasive, attributes that are critical for embryonic implantation ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…Although little is known about the precise role VGLL1 plays in placental development, aberrantly elevated expression of this gene has also been observed in several aggressive cancer types. Pancreatic, triple negative breast, gastric, and HPV-related cancers such as ovarian cancer show the highest levels of VGLL1 mRNA expression, and increased transcription of VGLL1 is strongly correlated with poor prognosis and lower overall patient survival ( 3 , 4 , 8 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes

Sonnemann,

Pazdrak,

Nassif

et al. 2024

Front. Oncol.

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IntroductionVestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists.MethodsThe aim of this study was to evaluate the cellular function and downstream genomic targets of VGLL1 in placental, pancreatic, and breast cancer cells. Functional assays were employed to assess the role of VGLL1 in cellular invasion and proliferation, and ChIP-seq and RNAseq assays were performed to identify VGLL1 target genes and potential impact using pathway analysis.ResultsChIP-seq analysis identified eight transcription factors with a VGLL1-binding motif that were common between all three cell types, including TEAD1-4, AP-1, and GATA6, and revealed ~3,000 shared genes with which VGLL1 interacts. Furthermore, increased VGLL1 expression led to an enhancement of cell invasion and proliferation, which was supported by RNAseq analysis showing transcriptional changes in several genes known to be involved in these processes.DiscussionThis work expands our mechanistic understanding of VGLL1 function in tumor cells and provides a strong rationale for developing VGLL1-targeted therapies for treating cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes

Sonnemann,

Pazdrak,

Nassif

et al. 2024

Front. Oncol.

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“…Evolutionary biology offers valuable insights into the origin of the gene, conservation and comparison of protein sequences among diverse species; reveals critical conserved regions, speciesdomain-substrate-specific functional significance [11][12][13]. WWP1 has variable gene and intron lengths but a relatively conserved exon structure and functional domains.…”

Section: Evolutionary History Of Wwp1mentioning

confidence: 99%

WWP1 E3 ligase at the crossroads of health and disease

Behera,

Reddy

2023

Cell Death Dis

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The E3 ubiquitin ligase WWP1 (WW Domain-containing E3 Ubiquitin Protein Ligase 1) is a member of the HECT (Homologous to the E6-associated protein Carboxyl Terminus) E3 ligase family. It is conserved across several species and plays crucial roles in various physiological processes, including development, cell growth and proliferation, apoptosis, and differentiation. It exerts its functions through ubiquitination or protein-protein interaction with PPXY-containing proteins. WWP1 plays a role in several human diseases, including cardiac conditions, neurodevelopmental, age-associated osteogenic disorders, infectious diseases, and cancers. In solid tumors, WWP1 plays a dual role as both an oncogene and a tumor suppressor, whereas in hematological malignancies such as AML, it is identified as a dedicated oncogene. Importantly, WWP1 inhibition using small molecule inhibitors such as Indole-3-Carbinol (I3C) and Bortezomib or siRNAs leads to significant suppression of cancer growth and healing of bone fractures, suggesting that WWP1 might serve as a potential therapeutic target for several diseases. In this review, we discuss the evolutionary perspective, structure, and functions of WWP1 and its multilevel regulation by various regulators. We also examine its emerging roles in cancer progression and its therapeutic potential. Finally, we highlight WWP1’s role in normal physiology, contribution to pathological conditions, and therapeutic potential for cancer and other diseases.

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WITHDRAWN: EIF4A3-regulated circGNAI2 inhibits the progression of triple-negative breast cancer by circGNAI2-miR-454-3p-VGLL4 axis

song,

Wang,

Peng

et al. 2023

Preprint

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Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer (BC) with high invasiveness, high rate of recurrence and metastasis, and poor prognosis. In this study, we demonstrated that circGNAI2 was lower expressed in TNBC tissues and cell lines. CircGNAI2 suppressed the proliferation and migration abilities of TNBC cells in vivo and in vitro. Of note, circGNAI2 can upregulate VGLL4 and inhibit the phosphorylation of STAT3 via sponging miR-454-3p. Moreover, circGNAI2 was downregulated by EIF4A3. Taken together, EIF4A3-regulated circGNAI2 could inhibit TNBC progression by regulating circGNAI2-miR-454-3p-VGLL4 axis and STAT3 signaling pathway, providing pivotal potential therapeutic targets for the treatment of TNBC.

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Vestigial-like 1 (VGLL1): An ancient co-transcriptional activator linking wing, placenta, and tumor development

Cited by 4 publications

References 83 publications

Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes

Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes

WWP1 E3 ligase at the crossroads of health and disease

WITHDRAWN: EIF4A3-regulated circGNAI2 inhibits the progression of triple-negative breast cancer by circGNAI2-miR-454-3p-VGLL4 axis

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