Mutations and Copy Number Abnormalities of Hippo Pathway Components in Human Cancers

He, Zhengjin; Li, Ruihan; Jiang, Hai

doi:10.3389/fcell.2021.661718

Cited by 10 publications

(10 citation statements)

References 63 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…58,59 . Finally, YAP1 has been shown to be associated with cancer progression and our study confirms that targeting YAP1 in this context could indeed be effective 60,61 .…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

The E-cadherin-ESR1-GRPR axis defines a sex-specific metastatic pathway in melanoma

Raymond

Pouteaux

Petit

et al. 2022

Preprint

View full text Add to dashboard Cite

Although tremendous progress has been made in understanding the mechanisms leading to cancer, those governing metastases are still poorly understood. E-cadherin (Ecad) is a cell-cell adhesion molecule essential for tissue homeostasis, and its loss often correlates with the dissemination of human cancers. However, whether and how the loss of Ecad triggers the full metastatic program is largely unknown. Here, we show that the loss of Ecad promotes melanoma lung metastases in females. The loss of Ecad, after the induction of estrogen receptor a; (ERa) expression, activates gastrin-releasing peptide receptor (GRPR) expression. GRPR promotes cellular processes essential for metastasis formation through Gaq and YAP1 signaling and its pharmacological inhibition reduces metastasis in vivo. This study reveals an Ecad-ERα-GRPR metastatic sex dimorphism axis in melanoma that is conserved in human breast cancer and provides proof of concept that the G-coupled receptor GRPR is a therapeutic target for metastasis.

show abstract

“…58,59 . Finally, YAP1 has been shown to be associated with cancer progression and our study confirms that targeting YAP1 in this context could indeed be effective 60,61 .…”

Section: Discussionsupporting

confidence: 80%

“…58, 59 . Finally, YAP1 has been shown to be associated with cancer progression and our study confirms that targeting YAP1 in this context could indeed be effective 60, 61 . Although targeting YAP1 may be effective for cancers that are not GRPR positive, its safety profile is likely to be lower than that of GRPR antagonists.…”

Section: Discussionsupporting

confidence: 80%

The E-cadherin-ESR1-GRPR axis defines a sex-specific metastatic pathway in melanoma

Raymond

Pouteaux

Petit

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that while Cai et al keenly appreciate the importance of their finding vis-a-vis the Hippo pathway in context – they appear unaware of the homozygous deletion of VGLL4 noted in the present publication. More broadly while the heterozygous deletion of VGLL4 is well known to the community due to high frequency 3p chromosome arm deletions (He et al, 2021) – even publications that have made detailed investigations into genetic alterations of the Hippo pathway did not discuss VGLL4 homozygous deletions (He et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

The puzzling case of the 3p25 homozygous deletion: the target is notVHLbutVGLL4andATG7

Muller,

Behr

2023

Preprint

View full text Add to dashboard Cite

The 3p25 locus experiences recurrent homozygous deletions in diverse carcinomas. A validated tumor suppressor gene (TSG),VHLhas long been assumed to be the target of this deletion.Here, we show that homozygous deletions at the 3p25 locus are common in renal clear cell carcinoma (RCC) and squamous cell carcinomas but that these do not center onVHLbut on two nearby overlapping genes,VGLL4andATG7. While hypomorphic mutations ofVHLcoupled with heterozygous deletions are undoubtedly a driver in RCC, DepMap CRISPR data indicate that the complete absence ofVHLis broadly detrimental to cancer cells. Re-examination of TCGA and PDX data calls into question whetherVHLis ever homozygous deleted, even in RCC.Instead, multiple lines of evidence support the homozygous deletion ofVGLL4as a driver event in squamous cell carcinomas and the homozygous deletion ofATG7as a driver in RCC, with important implication for precision oncology. VGLL4 is the major negative regulator of the YAP/TEAD complex, with elimination of VGLL4 leading to hyperactive oncogenic YAP-dependent transcriptional activity which could be targeted by clinically emerging YAP/TEAD inhibitors. ATG7 is a critical regulator of autophagy, limiting proliferation in conditions of nutrient limitation and its deletion may open novel vulnerabilities for synthetic lethality.

show abstract

“…It integrates various parameters such as cell polarity, cell contact, and G-protein coupled receptor signaling to fine-tune cell proliferation and survival. Defects of the SWH pathway are associated with poor prognosis in many cancers and are thought to help cancer cells escape cell 'contact inhibition' [88,89].…”

Section: The Salvador-warts-hippo Pathway: When the Brake Breaksmentioning

confidence: 99%

RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

Dillard

Reis

Rusten

2021

IJMS

View full text Add to dashboard Cite

The phenomenon of how oncogenes and tumor-suppressor mutations can synergize to promote tumor fitness and cancer progression can be studied in relatively simple animal model systems such as Drosophila melanogaster. Almost two decades after the landmark discovery of cooperative oncogenesis between oncogenic RasV12 and the loss of the tumor suppressor scribble in flies, this and other tumor models have provided new concepts and findings in cancer biology that has remarkable parallels and relevance to human cancer. Here we review findings using the RasV12; scrib−/− tumor model and how it has contributed to our understanding of how these initial simple genetic insults cooperate within the tumor cell to set in motion the malignant transformation program leading to tumor growth through cell growth, cell survival and proliferation, dismantling of cell–cell interactions, degradation of basement membrane and spreading to other organs. Recent findings have demonstrated that cooperativity goes beyond cell intrinsic mechanisms as the tumor interacts with the immediate cells of the microenvironment, the immune system and systemic organs to eventually facilitate malignant progression.

show abstract

Mutations and Copy Number Abnormalities of Hippo Pathway Components in Human Cancers

Cited by 10 publications

References 63 publications

The E-cadherin-ESR1-GRPR axis defines a sex-specific metastatic pathway in melanoma

The E-cadherin-ESR1-GRPR axis defines a sex-specific metastatic pathway in melanoma

The puzzling case of the 3p25 homozygous deletion: the target is notVHLbutVGLL4andATG7

RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

Contact Info

Product

Resources

About