High Yes-associated protein 1 with concomitant negative LATS1/2 expression is associated with poor prognosis of advanced gastric cancer

Kim, Eojin; Ahn, Bokyung; Oh, Harim; Lee, Yoo Jin; Lee, Ju Han; Kim, Chul‐Hwan; Chae, Yang Seok; Kim, Joo Young

doi:10.1016/j.pathol.2019.01.001

Cited by 18 publications

(24 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This might support the previously reported tumor suppressive role of VGLL4 and consistent with previous studies of correlation between VGLL4 expression and favorable clinicopathologic factors (10, 13). High expression of YAP and TEAD4 was identified in 138 (46.8%) and 144 (48.8%) cases, respectively and significantly associated with aggressive clinicopathologic factors such as presence of lymphovascular invasion, lymph node metastasis, and distant metastasis, as previously described (15, 21).…”

Section: Discussionsupporting

confidence: 68%

“…In addition, TEAD4 has been reported to be highly expressed in various cancers including colorectal cancer in previous studies (9, 20). The high expression of YAP and TEAD4 has been illustrated in various cancers and those expressions were correlated with adverse clinicopathologic factors and poor clinical outcomes (7, 15, 16, 19, 21). VGLL has been recently emerged as a transcriptional cofactor having tumor suppressive role in some kind of cancers, including lung, colon, and gastric cancers (10, 11, 13).…”

Section: Discussionmentioning

confidence: 99%

“…The results of immunohistochemistry for VGLL4, YAP, and TEAD were evaluated as previously described (13, 15). The nuclear expressions were scored, irrespective of cytoplasmic expression, by multiplying the intensity of stained cells (0, none; 1+, weak; 2+, moderate; 3+, strong) and the proportion (0, none; 1, 1–25%; 2, >25–50%; 3, >50–75%; 4, >75%), ranging from 0 to 12.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

VGLL4 with low YAP expression is associated with favorable prognosis in colorectal cancer

Kim

Lee

et al. 2020

APMIS

Self Cite

View full text Add to dashboard Cite

The Hippo pathway is a tumor suppressive pathway regulating Yes-associated protein-TEA domain-containing sequence-specific transcription factor (YAP-TEAD) complex. VGLL (Vestigial-like) proteins are transcriptional cofactors competing with YAP for TEAD binding and interfering oncogenic activity of YAP-TEAD complex. We evaluated the expression of VGLL4, YAP, and TEAD4 and assessed their correlations with clinicopathologic factors and prognostic effects in 295 colorectal cancers. VGLL4 was positive in 164 (55.6%) cases and correlated with small tumor size, low pT classification, and absence of lymph node metastasis. YAP and TEAD4 were highly expressed in 138 (46.8%) cases and 144 (48.8%) cases, respectively, and high expressions were associated with presence of lymphovascular invasion and lymph node metastasis, or distant metastasis. VGLL4 expression was significantly correlated with low YAP expression (p < 0.001) and had significantly better overall survival than negative expression (p < 0.001). High YAP (HR, 2.108; 95% confidence interval, 1.239-3.584; p = 0.006) and TEAD4 (1.724; 1.021-2.912; p = 0.042) expressions were associated with poor overall survivals. The combined VGLL4 pos YAP low expression showed the best overall survival than other groups (p < 0.001). VGLL4 expression (0.381; 0.212-0.683; p = 0.001) and combined VGLL4 pos YAP low expression (0.227; 0.108-0.475; p < 0.001) were independent good prognostic factors in colorectal cancers. The expressions of VGLL4, YAP, and TEAD4 can be used as prognostic markers in colorectal cancer patients.

show abstract

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

VGLL4 with low YAP expression is associated with favorable prognosis in colorectal cancer

Kim

Lee

et al. 2020

APMIS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although it is a controversial notion that YAP overexpression alone is related to the development of GC, several studies have identified YAP1 as an oncoprotein in the stomach. In normal and proliferating normal gastric epithelium, low or moderate levels of YAP1 expression are detected, whereas significantly elevated YAP1 levels are consistently observed in both primary and metastatic GC [23,24]. YAP1 expression is strongly positively correlated with lymphatic metastasis and shortened overall survival time, indicating that YAP may be used as an independent prognostic marker for GC [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

RP11-323N12.5 promotes the malignancy and immunosuppression of human gastric cancer by increasing YAP1 transcription

et al. 2020

View full text Add to dashboard Cite

Background YAP1 is a core protein of the Hippo signaling pathway and is associated with malignancy and immunosuppression. In the present study, we discovered a novel lncRNA, RP11-323N12.5, with tumor promotion and immunosuppression activities through enhancing transcription of YAP1. Methods RP11-323N12.5 was identified using GEPIA. Its expression levels and their relationship with clinical features were investigated using clinical samples. The regulation of YAP1 transcription by RP11-323N12.5 was investigated in both GC and T cells, the tumor and immunosuppression promotion roles of RP11-323N12.5 were explored in vitro and in vivo. Results RP11-323N12.5 was the most up-regulated lncRNA in human GC, based on data from the TCGA database. Its transcription was significantly positively correlated with YAP1 transcription, YAP1 downstream gene expression which contribute to tumor growth and immunosuppression. RP11-323N12.5 promoted YAP1 transcription by binding to c-MYC in the YAP1 promoter region. Meanwhile, transcription of RP11-323N12.5 was also regulated by YAP1/TAZ/TEADs activation in GC cells. RP11-323N12.5 had tumor-and immnosuppression-promoting effects by enhancing YAP1 downstream genes in GC cells. Excessive RP11-323N12.5 was also observed in tumor-infiltrating leukocytes (TILs), which may be exosomederived and also be related to enhanced Treg differentiation as a result YAP1 up-regulation. Moreover, RP11-323N12.5 promoted tumor growth and immunosuppression via YAP1 up-regulation in vivo. Conclusions RP11-323N12.5 was the most up-regulated lncRNA in human GC and it promoted YAP1 transcription by binding to c-MYC within the YAP1 promoter in both GC and T cells. RP11-323N12.5 is an ideal therapeutic target in human GC due to its tumor-promoting and immunosuppression characteristics.

show abstract

“…YAP is a transcriptional cofactor that controls oncogenic functions such as growth factor‐independent cellular proliferation, epithelial‐mesenchymal transition, cellular invasion, and metastasis [10, 11]. Nuclear YAP immunolabeling is associated with aggressive clinicopathologic behavior with poor prognosis in several types of cancers including gastric, cervix, ovary, and breast cancers [12–17]. Recently, Garcia et al.…”

mentioning

confidence: 99%

High YAP and TEAD4 immunolabelings are associated with poor prognosis in patients with gallbladder cancer

Kim

Sung

Hong

2021

APMIS

Self Cite

View full text Add to dashboard Cite

Yes‐associated protein (YAP) and TEA domain‐containing sequence‐specific transcription factors 4 (TEAD4) are essential components of the Hippo pathway. Abnormal regulation of the Hippo pathway contributes to the progression and metastasis of many cancer types. However, their clinicopathologic and prognostic significances have not been studied in gallbladder cancers. Here, we systematically evaluated the YAP and TEAD4 immunolabelings and their association with clinicopathologic characteristics and survival outcomes using 212 specimens of surgically resected gallbladder cancers. High YAP and TEAD4 immunolabelings were identified in 70 (33%) cases and were associated with infiltrative growth pattern, poor differentiation, perineural invasion, and advanced pT classification and AJCC stage. High YAP immunolabeling was significantly associated with high TEAD4 immunolabeling (p < 0.001). High immunolabeling levels of YAP or TEAD4 alone and the combined YAPhigh TEAD4high group were significantly associated with poor survival in both univariate (p < 0.001) and multivariate analyses (HR = 2.358; 95% CI, 1.369–4.061; p = 0.002). Therefore, the YAP and TEAD4 immunolabelings are associated with aggressive behavior of gallbladder cancers and may be useful as a prognostic indicator in patients with surgically resected gallbladder cancer.

show abstract

High Yes-associated protein 1 with concomitant negative LATS1/2 expression is associated with poor prognosis of advanced gastric cancer

Cited by 18 publications

References 40 publications

VGLL4 with low YAP expression is associated with favorable prognosis in colorectal cancer

VGLL4 with low YAP expression is associated with favorable prognosis in colorectal cancer

RP11-323N12.5 promotes the malignancy and immunosuppression of human gastric cancer by increasing YAP1 transcription

High YAP and TEAD4 immunolabelings are associated with poor prognosis in patients with gallbladder cancer

Contact Info

Product

Resources

About