Functional significance of Hippo/YAP signaling for drug resistance in colorectal cancer

Song, Ruolan; Gu, Dongsheng; Zhang, Lining; Zhang, Xiaoli; Yu, Beiqin; Liu, Bingya; Xie, Jingwu

doi:10.1002/mc.22883

Cited by 39 publications

(38 citation statements)

References 35 publications

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“…Similarly, Wang et al 34 reported that YAP expression was highest in HCT116, LS174T, LoVo, SW480 and SW620 colon cancer cell lines and that the capacity of these cells for proliferation, metastasis and invasion was markedly reduced by silencing YAP expression. In addition, YAP has been identified as a driver gene for EMT, which may contribute to the invasion and metastasis of cancers, 20,35 including gastric cancer, 36 breast cancer 37 and pancreatic cancer. [38][39][40] The results of the present study conclusively demonstrate that the SNHG11-induced malignant behaviour of CRC is accompanied by alterations in YAP phosphorylation and total YAP protein levels.…”

Section: Discussionmentioning

confidence: 99%

Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer

Zhou

Wang

et al. 2019

Intl Journal of Cancer

140

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality worldwide. Emerging evidence indicates that tumour cells release substantial amounts of RNA into the bloodstream, in which RNA strongly resists RNases and is present at sufficient levels for quantitative analyses. Our study aimed to discover blood‐based markers for the early detection of CRC and to ascertain their efficiency in discriminating healthy controls, patients with polyps and adenomas and cancer patients. We first analysed and screened ZFAS1, SNHG11, LINC00909 and LINC00654 in a bioinformatics database and then collected clinical plasma samples for preliminary small‐scale analysis and further large‐scale verification. We then explored the mechanism of dominant lncRNA SNHG11 expression in CRC by in vitro and in vivo assays. The combination of ZFAS1, SNHG11, LINC00909 and LINC00654 showed high diagnostic performance for CRC (AUC: 0.937), especially early‐stage disease (AUC: 0.935). Plasma levels of the four candidate lncRNAs were significantly reduced in postoperative samples compared to preoperative samples. A panel including these four lncRNAs performed well in distinguishing patient groups with different stages of colon disease, and SNHG11 exhibited the greatest diagnostic ability to identify precancerous lesions and early‐stage tumour formation. Mechanistically, high SNHG11 expression promotes proliferation and metastasis by targeting the Hippo pathway. Taken together, the data indicate that SNHG11 may be a novel therapeutic target for the treatment of CRC and a potential biomarker for the early detection of CRC.

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Section: Discussionmentioning

confidence: 99%

Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer

Zhou

Wang

et al. 2019

Intl Journal of Cancer

140

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“…The Hippo signaling pathway, first identified in Drosophila, was originally discovered to play a crucial role in regulating tissue growth; gradually it was found to be closely implicated in the modulation of multiple biological processes such as cell proliferation and apoptosis. [4][5][6][7] Mst1/2 (Mammalian Ste20-like 1 and 2), LATS1/2 (large tumor suppressor kinase 1/2), MOB1A/1B (MOB kinase activator 1A/1B) and SAV1 (salvador family WW domain-containing protein 1) are core components of Hippo signaling pathway, and their main role is to prevent the transportation of Yes-associated protein (YAP) to nuclear, thereby inhibiting the transcription of its downstream genes. 8,9 Notably, studies have confirmed that Hippo/YAP signaling plays a crucial role in chemoradiotherapy resistance of tumors.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Notably, studies have confirmed that Hippo/YAP signaling plays a crucial role in chemoradiotherapy resistance of tumors. For example, Song et al 7 found that knockdown of YAP1 significantly enhanced the sensitivity of colorectal cancer LoVo-R cells, an acquired 5-fluorouracil resistant cell line. Fernandez et al 10 demonstrated that YAP conferred tumor cell radio-resistance and promoted cell ongoing proliferation after radiation in medulloblastoma.…”

Section: Introductionmentioning

confidence: 99%

<p>Role of Hippo/YAP signaling in irradiation-induced glioma cell apoptosis</p>

Chen

Wang

et al. 2019

CMAR

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Background: Although Hippo/Yes-associated protein (YAP) signaling plays crucial roles in radiation sensitivity and resistance of multiple kinds of cancers, its role in the radiation sensitivity of glioma cells remains unclear. The present study aimed to reveal Hippo/YAP role in the radiation sensitivity of glioma cells. Methods: Glioma U251 cells were administrated with different doses of irradiation. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were used to assess cell viability and apoptosis. Co-immunoprecipitation (co-IP) assay was used to assess the interactions between proteins. Results: The results showed that irradiation exposure significantly inhibited cell viability and induced cell apoptosis in a dose-dependent manner, as well as decreased YAP1 expression via enhancing RCHY1-mediated YAP1 protein degradation. In addition, we observed that downregulation of YAP1 or RCHY1 weakened the role of irradiation exposure in cell viability inhibition and apoptosis promotion. Conclusion: Collectively, this study emphasizes the vital role of Hippo/YAP signaling in radiation sensitivity of glioma, that RCHY1-mediated YAP1 protein downregulation is a main mechanism accounting for radiation-induced glioma cell apoptosis. Our study may enrich the theoretical basis of Hippo/YAP signaling as a new target for improving radiation sensitivity in glioma.

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“…YAP1 was known to be associated with therapy resistance of cancer treatment [16]. A number of studies demonstrated that increased nuclear localization of YAP-TAZ and higher transcriptional activities of YAP/TAZ target genes have been observed in therapyresistant tumors [16,29,30]. With regard to the relationship between YAP1 and PCa, Jiang et al conducted a mass spectrometry-based quantitative proteomic approach and used it to compare protein phosphorylation in orthotopic xenograft tumors grown in either intact or castrated mice [31].…”

Section: Discussionmentioning

confidence: 99%

Impact of nuclear YAP1 expression in residual cancer after neoadjuvant chemohormonal therapy with docetaxel for high-risk localized prostate cancer

et al. 2020

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Background: Although docetaxel-based chemohormonal therapy (CHT) is one of the standard treatments for castration-resistant prostate cancer (CRPC), pertinent biomarkers and precise mechanisms involved in the resistance for CHT for CRPC remain unknown. We investigated the relationship between chemohormonal resistance and the expression of steroid receptors and Hippo pathway proteins using a docetaxel-resistant prostate cancer (PCa) cell line and human PCa tissues in patients who underwent surgery with and without neoadjuvant therapy. Methods: A docetaxel-resistant subline (22Rv1-DR) was generated to assess Hippo pathway protein expression and the effect of YAP1 inhibition on cellular characteristics. A tissue microarray with 203 cores from 70 high-risk localized PCa tissues was performed to assess steroid receptor and Hippo pathway protein expressions. Results: Nuclear YAP (nYAP) expression was higher in 22RV-1-DR than in parental 22Rv-1 and YAP1 knockdown suppressed cell proliferation of 22Rv1-DR. Steroid receptor and Hippo pathway protein expressions varied among three different neoadjuvant groups, and nYAP1 expression was the highest in the CHT group. The patients with high nYAP in residual cancer after neoadjuvant CHT had a significantly higher biochemical recurrence (BCR) rate than those with low nYAP1. On multivariate analysis, the high nYAP1 was an independent prognostic factor for BCR. Conclusions: nYAP expression is a potential biomarker in high-risk patients treated with docetaxel-based CHT. Steroid receptors and Hippo pathway proteins may play a role in the chemohormonal resistance in advanced PCa.

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Functional significance of Hippo/YAP signaling for drug resistance in colorectal cancer

Cited by 39 publications

References 35 publications

Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer

Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer

<p>Role of Hippo/YAP signaling in irradiation-induced glioma cell apoptosis</p>

Impact of nuclear YAP1 expression in residual cancer after neoadjuvant chemohormonal therapy with docetaxel for high-risk localized prostate cancer

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