YAP1 is a potent driver of the onset and progression of oral squamous cell carcinoma.

Published on Mar 18, 2020in Science Advances11.5
· DOI :10.1126/SCIADV.AAY3324
Hirofumi Omori (Kobe University), Hirofumi Omori3
Estimated H-index: 3
(Kobe University)
+ 15 AuthorsHiroki Hikasa8
Estimated H-index: 8
Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common group of cancers in the world, and patients have a poor prognosis. Here, we present data indicating that YAP1 may be a strong driver of the onset and progression of oral SCC (OSCC), a major subtype of HNSCC. Mice with tongue-specific deletion of Mob1a/b and thus endogenous YAP1 hyperactivation underwent surprisingly rapid and highly reproducible tumorigenesis, developing tongue carcinoma in situ within 2 weeks and invasive SCC within 4 weeks. In humans, precancerous tongue dysplasia displays YAP1 activation correlating with reduced patient survival. Combinations of molecules mutated in OSCC may increase and sustain YAP1 activation to the point of oncogenicity. Strikingly, siRNA or pharmacological inhibition of YAP1 blocks murine OSCC onset in vitro and in vivo. Our work justifies targeting YAP1 as therapy for OSCC and perhaps HNSCC, and our mouse model represents a powerful tool for evaluating these agents.
  • References (41)
  • Citations (0)
📖 Papers frequently viewed together
7 Citations
1 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1C.R. Leemans (VUmc: VU University Medical Center)H-Index: 67
#2Peter J.F. Snijders (VUmc: VU University Medical Center)H-Index: 94
Last. Ruud H. Brakenhoff (VUmc: VU University Medical Center)H-Index: 46
view all 3 authors...
The article as originally published contained errors in Figure 3. The direction of the arrows associated with the labels for p53 and RB were incorrect. This has now been corrected in all versions of the article.
1 CitationsSource
#1Daniel Martin (NIH: National Institutes of Health)H-Index: 21
#2Maria Sol Degese (NIH: National Institutes of Health)H-Index: 8
Last. J. Silvio Gutkind (UCSD: University of California, San Diego)H-Index: 87
view all 21 authors...
Dysregulation of the Hippo signaling pathway and the consequent YAP1 activation is a frequent event in human malignancies, yet the underlying molecular mechanisms are still poorly understood. A pancancer analysis of core Hippo kinases and their candidate regulating molecules revealed few alterations in the canonical Hippo pathway, but very frequent genetic alterations in the FAT family of atypical cadherins. By focusing on head and neck squamous cell carcinoma (HNSCC), which displays frequent FA...
18 CitationsSource
#2Carmen Segrelles (Complutense University of Madrid)H-Index: 21
Last. Corina Lorz (Complutense University of Madrid)H-Index: 25
view all 13 authors...
Abstract Objectives Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved. Mat...
8 CitationsSource
#1Hiroki Goto (Kobe University)H-Index: 1
#2Miki Nishio (Kobe University)H-Index: 13
Last. Akira Suzuki (Kobe University)H-Index: 67
view all 14 authors...
ABSTRACT Hippo signaling is modulated in response to cell density, external mechanical forces, and rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and influence Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the...
11 CitationsSource
#1Noa Furth (Weizmann Institute of Science)H-Index: 6
#2Yael Aylon (Weizmann Institute of Science)H-Index: 23
Last. Moshe Oren (Weizmann Institute of Science)H-Index: 108
view all 3 authors...
Abstract The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module c...
13 CitationsSource
Most of the studies dealing with Chronic Mechanical Irritation (CMI) and Oral Cancer (OC) only considered prosthetic and dental variables separately, and CMI functional factors are not registered. Thus, the aim of this study was to assess OC risk in individuals with dental, prosthetic and functional CMI. Also, we examined CMI presence in relation to tumor size. A case-control study was carried out from 2009 to 2013. Study group were squamous cell carcinoma cases; control group was patients seeki...
#1Lorena VerduciH-Index: 4
#2Maria FerraiuoloH-Index: 15
Last. Giovanni BlandinoH-Index: 48
view all 11 authors...
Circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about their role in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC. Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with pa...
42 CitationsSource
#1Young Gyu Eun (Kyung Hee University)H-Index: 12
#2Dong Jin Lee (Hallym University)H-Index: 5
Last. Hyuk-JoonLeeH-Index: 188
view all 8 authors...
// Young-Gyu Eun 1, 2 , Dongjin Lee 1, 3 , Young Chan Lee 2 , Bo Hwa Sohn 1 , Eui Hyun Kim 1, 4 , Sun Young Yim 1, 5 , Kee Hwan Kwon 3 and Ju-Seog Lee 1 1 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, Republic of Korea 3 Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Hallym University, Seoul, Republic of Korea 4 De...
6 CitationsSource
#1Stephano S. Mello (Stanford University)H-Index: 16
#2Liz J. Valente (Stanford University)H-Index: 8
Last. Laura D. Attardi (Stanford University)H-Index: 42
view all 20 authors...
Summary The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, which have remained elusive, we analyzed pancreatic cancer development in mice expressing p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p53 53,54 TAD2 mutant behaves as a "super-tumor suppressor," with an enhanced capacity to both suppress pancreatic cancer and transactivate select p53 target genes, including Ptpn14 . Ptpn1...
30 CitationsSource
#1Athanassios Argiris (Thomas Jefferson University)H-Index: 41
#2Kevin J. Harrington (ICR: Institute of Cancer Research)H-Index: 67
Last. LicitraLisa (University of Milan)H-Index: 46
view all 7 authors...
The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy, followed by maintenance cetuximab (the “EXTREME” regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies and it confers well-documented survival benefits, with median survival approximately ranging b...
35 CitationsSource
Cited By0