Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice

Nishio, Makoto; To, Yoko; Maehama, Tomohiko; Aono, Yukari; Otani, Junji; Hikasa, Hiroki; Kitagawa, Akihiro; Mimori, Koshi; Sasaki, Takehiko; Nishina, Hiroshi; Toyokuni, Shinya; Lydon, John P.; Nakao, Kazuwa; Mak, Tak W.; Kiyono, Tohru; Katabuchi, Hidetaka; Tashiro, Hironori; Suzuki, Akira

doi:10.1111/cas.14581

Cited by 27 publications

(33 citation statements)

References 54 publications

(76 reference statements)

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“…A 2nd reason for early SCC onset in Hippo‐mutant mice may be elevated production of BMP4, a soluble growth factor that also regulates ΔNp63 69 . Indeed, we detected increased BMP4 in Mob1 ‐deficient tongue and cervical epithelial cells compared to controls 33,42 . A 3rd reason for our findings may be potential positive feedback between YAP1 and EGF signaling.…”

Section: Putative Mechanism By Which Hippo/yap Signaling Drives Scc Omentioning

confidence: 54%

“…In addition, as detailed above, loss‐of‐function or gain‐of‐function mutations of genes that result in YAP activation are linked to SCCs 62,65‐67 . When these gene mutations combine with carcinogens, YAP1 activity rises even higher 33,42 . In short, there is substantial evidence supporting our hypothesis that, for many SCCs, the original CIS is caused by a simple sustaining of YAP1 activity over a particular threshold.…”

Section: Putative Mechanism By Which Hippo/yap Signaling Drives Scc Omentioning

confidence: 59%

“…62,[65][66][67] When these gene mutations combine with carcinogens, YAP1 activity rises even higher. 33,42 In short, there is substantial evidence supporting our hypothesis that, for many SCCs, the original CIS Conversely, all EGF-like ligands can apparently activate YAP1, 62 so that an autocrine loop related to YAP1-EGF/EGFR signaling may stimulate SCC genesis and progression. A 4th contributor to our results may be an interaction between YAP1 and cell adhesion genes.…”

Section: Putative Mechanis M By Whi Ch Hipp O/ Yap S I G Naling Drimentioning

confidence: 65%

“…In contrast, transgenic (Tg) mice showing modest activation of YAP (S127A), a constitutively active mutant form of YAP1, exhibit invasive CvSCC only after 6‐8 mo 41 . Tg mice that both lack YAP1 and express HPV16 under the control of the K14 promoter do not show the cervical phenotype of HPV16 Tg mice alone 42 . The HPV E6 protein prevents the YAP1 protein from undergoing proteasome‐mediated degradation 41 .…”

Section: Links Between Hippo‐yap Signaling and Scc Onsetmentioning

confidence: 99%

“…HPV E7 protein binds to and targets PTPN14 for proteasome‐mediated degradation, which likely relieves the cytoplasmic retention of YAP by PTPN14 43,44 . This combination of HPV E6/E7‐induced accumulation of YAP protein plus its release to the nucleus leads to vigorous YAP activation that may promote human cervical epithelial cell proliferation and eventually CIS onset 23,42 . HPV E6 also inhibits p53, spurring the progression of CIS to invasive CvSCC.…”

Section: Links Between Hippo‐yap Signaling and Scc Onsetmentioning

confidence: 99%

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The role of Hippo‐YAP signaling in squamous cell carcinomas

et al. 2020

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Stratified squamous epithelium (SSE) consists of layers of squamous epithelial cells arranged over top of a basement membrane. The outermost layers of the nasal-oral cavity, esophagus, trachea, bronchi, cervix, vagina, and skin are all SSE. SSE constantly interacts with various stimuli, including harmful stresses. In so doing, SSE becomes the origin of several human malignancies, including esophageal squamous cell carcinoma (ESCC), head-and-neck SCC (HNSCC), cutaneous (skin) SCC (CuSCC), lung SCC (LSCC), and cervical SCC (CvSCC), which are among the most common forms of human cancers. This transformation is often associated with dysregulation of the Hippo-YAP intracellular signaling pathway. In this review, we provide an overview of how Hippo-YAP signaling drives SCC onset and development and discuss how this knowledge might lead to new therapeutic avenues for these insidious cancers.

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Section: Putative Mechanism By Which Hippo/yap Signaling Drives Scc Omentioning

confidence: 54%

Section: Putative Mechanism By Which Hippo/yap Signaling Drives Scc Omentioning

confidence: 59%

Section: Putative Mechanis M By Whi Ch Hipp O/ Yap S I G Naling Drimentioning

confidence: 65%

Section: Links Between Hippo‐yap Signaling and Scc Onsetmentioning

confidence: 99%

Section: Links Between Hippo‐yap Signaling and Scc Onsetmentioning

confidence: 99%

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The role of Hippo‐YAP signaling in squamous cell carcinomas

et al. 2020

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Human papillomaviruses: Knowns, mysteries, and unchartered territories

Gelbard,

Munger

2023

Journal of Medical Virology

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There has been an explosion in the number of papillomaviruses that have been identified and fully sequenced. Yet only a minute fraction of these has been studied in any detail. Most of our molecular research efforts have focused on the E6 and E7 proteins of “high‐risk,” cancer‐associated human papillomaviruses (HPVs). Interactions of the high‐risk HPV E6 and E7 proteins with their respective cellular targets, the p53 and the retinoblastoma tumor suppressors, have been investigated in minute detail. Some have thus questioned if research on papillomaviruses remains an exciting and worthwhile area of investigation. However, fundamentally new insights on the biological activities and cellular targets of the high‐risk HPV E6 and E7 proteins have been discovered and previously unstudied HPVs have been newly associated with human diseases. HPV infections continue to be an important cause of human morbidity and mortality and since there are no antivirals to combat HPV infections, research on HPVs should remain attractive to new investigators and biomedical funding agencies, alike.

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Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Ye,

Zheng,

et al. 2023

MedComm

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Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high‐risk HPV infection can result in cervical precancerous lesions and cervical cancer, with 70% of cervical cancer cases associated with high‐risk types HPV16 and 18. HPV infection imposes a significant financial and psychological burden. Therefore, studying methods to eradicate HPV infection and halt the progression of precancerous lesions remains crucial. This review comprehensively explores the mechanisms underlying HPV‐related cervical lesions, including the viral life cycle, immune factors, epithelial cell malignant transformation, and host and environmental contributing factors. Additionally, we provide a comprehensive overview of treatment methods for HPV‐related cervical precancerous lesions and cervical cancer. Our focus is on immunotherapy, encompassing HPV therapeutic vaccines, immune checkpoint inhibitors, and advanced adoptive T cell therapy. Furthermore, we summarize the commonly employed drugs and other nonsurgical treatments currently utilized in clinical practice for managing HPV infection and associated cervical lesions. Gene editing technology is currently undergoing clinical research and, although not yet employed officially in clinical treatment of cervical lesions, numerous preclinical studies have substantiated its efficacy. Therefore, it holds promise as a precise treatment strategy for HPV‐related cervical lesions.

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Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 27 publications

References 54 publications

The role of Hippo‐YAP signaling in squamous cell carcinomas

The role of Hippo‐YAP signaling in squamous cell carcinomas

Human papillomaviruses: Knowns, mysteries, and unchartered territories

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

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