Distinct Changes in the Expression TAZ are Associated with Normal Cervix and Human Cervical Cancer

Liu, Yaofang; Ren, Mulan; Tan, Xiaoyong; Hu, Lina

doi:10.7150/jca.26623

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…In addition, the regulatory factor Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) can also be activated by LPA4/LPA6 via the Gα12/Gα13 signaling pathway [35]. YAP and TAZ can accelerate the progression of cancer by promoting the proliferation and migration of cancer cells, such as accelerating liver cancer, bladder cancer and lung cancer [36][37][38]. Also, the volume, number and thickness of trabeculae increased in adult LPA4 -/mice, contrary to those observed in LPA 1 -/mice, suggesting that LPA 4 has a negative regulatory effect on bone formation and can counteract LPA 1 -induced bone formation [39].…”

Section: Lpar4mentioning

confidence: 99%

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

Xiang¹,

Lü²,

Shao³

et al. 2020

J. Cancer

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Lysophosphatidic acid (LPA, 1-acyl-2-hemolytic-sn-glycerol-3-phosphate) extracted from membrane phospholipid is a kind of simple bioactive glycophospholipid, which has many biological functions such as stimulating cell multiplication, cytoskeleton recombination, cell survival, drug-fast, synthesis of DNA and ion transport. Current studies have shown that six G-coupled protein receptors (LPAR1-6) can be activated by LPA. They stimulate a variety of signal transduction pathways through heterotrimeric G-proteins (such as Gα12/13, Gαq/11, Gαi/o and GαS). LPA and its receptors play vital roles in cancers, nervous system diseases, cardiovascular diseases, liver diseases, metabolic diseases, etc. In this article, we discussed the structure of LPA receptors and elucidated their functions in various diseases, in order to better understand them and point out new therapeutic schemes for them.

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Section: Lpar4mentioning

confidence: 99%

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

Xiang¹,

Lü²,

Shao³

et al. 2020

J. Cancer

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show abstract

“…A small number of previous studies have analysed the role of TAZ in cervical cancer; however, their findings are controversial. One study identified that TAZ expression is decreased in cervical cancer compared with normal tissue 17 . In contrast, others suggest that TAZ is oncogenic and regulates proliferation, invasion and apoptosis whilst also upregulating PD-L1, a prominent regulator of T-cell evasion 18 .…”

Section: Introductionmentioning

confidence: 99%

The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer

Patterson,

Cogan,

Cassidy

et al. 2024

Nat Commun

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Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies. The Hippo signalling pathway is important in HPV+ cancers, with the downstream effector YAP playing a pro-oncogenic role. In contrast, the significance of its paralogue TAZ remains largely uncharacterised in these cancers. We demonstrate that TAZ is dysregulated in a HPV-type dependent manner by a distinct mechanism to that of YAP and controls proliferation via alternative cellular targets. Analysis of cervical cancer cell lines and patient biopsies revealed that TAZ expression was only significantly increased in HPV18+ and HPV18-like cells and TAZ knockdown reduced proliferation, migration and invasion only in HPV18+ cells. RNA-sequencing of HPV18+ cervical cells revealed that YAP and TAZ have distinct targets, suggesting they promote carcinogenesis by different mechanisms. Thus, in HPV18+ cancers, YAP and TAZ play non-redundant roles. This analysis identified TOGARAM2 as a previously uncharacterised TAZ target and demonstrates its role as a key effector of TAZ-mediated proliferation, migration and invasion in HPV18+ cancers.

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Cancer/testis-45A1 promotes cervical cancer cell tumorigenesis and drug resistance by activating oncogenic SRC and downstream signaling pathways

Meng,

Guo,

Chen

et al. 2023

Cell Oncol.

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Background Cancer/testis antigen-45A1 (CT45A1) is overexpressed in various types of cancer but is not expressed in healthy women. The role of CT45A1 in cervical cancer has not yet been described in the literature. Purpose The aim of this research was to study the role of CT45A1 in cervical cancer progression and drug resistance, elucidate the mechanisms underlying CT45A1-mediated tumorigenesis and investigate CT45A1 as a biomarker for cervical cancer diagnosis, prognostic prediction, and targeted therapy. Methods The CT45A1 levels in the tumors from cervical cancer patients were measured using immunohistochemical staining. The role and mechanisms underlying CT45A1-mediated cervical cancer cell tumor growth, invasion, and drug resistance were studied using xenograft mice, cervical cancer cells, immunohistochemistry, RNA-seq, real-time qPCR, Chromatin immunoprecipitation and Western blotting. Results CT45A1 levels were notably high in the tumor tissues of human cervical cancer patients compared to the paracancerous tissues (p < 0.001). Overexpression of CT45A1 was closely associated with poor prognosis in cervical cancer patients. CT45A1 promoted cervical cancer cell tumor growth, invasion, neovascularization, and drug resistance. Mechanistically, CT45A1 promoted the expression of 128 pro-tumorigenic genes and concurrently activated key signaling pathways, including the oncogenic SRC, ERK, CREB, and YAP/TAZ signaling pathways. Furthermore, CT45A1-mediated tumorigenesis and drug resistance were markedly inhibited by the small molecule lycorine. Conclusion CT45A1 promotes cervical cancer cell tumorigenesis, neovascularization, and drug resistance by activating oncogenic SRC and downstream tumorigenic signaling pathways. These findings provide new insight into the pathogenesis of cervical cancer and offer a new platform for the development of novel therapeutics against cervical cancer.

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Distinct Changes in the Expression TAZ are Associated with Normal Cervix and Human Cervical Cancer

Cited by 5 publications

References 28 publications

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer

Cancer/testis-45A1 promotes cervical cancer cell tumorigenesis and drug resistance by activating oncogenic SRC and downstream signaling pathways

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