The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma

Publication date: 3 September 2019Source: Cell Reports, Volume 28, Issue 10Author(s): Wen-Hsuan Yang, Chien-Kuang Cornelia Ding, Tianai Sun, Gabrielle Rupprecht, Chao-Chieh Lin, David Hsu, Jen-Tsan ChiSummaryDespite recent advances, the poor outcomes in renal cell carcinoma (RCC) suggest novel therapeutics are needed. Ferroptosis is a form of regulated cell death, which may have therapeutic potential toward RCC; however, much remains unknown about the determinants of ferroptosis susceptibility. We found that ferroptosis susceptibility is highly influenced by cell density and confluency. Because cell density regulates the Hippo-YAP/TAZ pathway, we investigated the roles of the Hippo pathway effectors in ferroptosis. TAZ is abundantly expressed in RCC and undergoes density-dependent nuclear or cytosolic translocation. TAZ removal confers ferroptosis resistance, whereas overexpression of TAZS89A sensitizes cells to ferroptosis. Furthermore, TAZ regulates the expression of Epithelial Membrane Protein 1 (EMP1), which, in turn, induces the expression of nicotinamide adenine dinucleotide phosphate (NADPH) Oxidase 4 (NOX4), a renal-enriched reactive oxygen species (ROS)-generating enzyme essential for ferroptosis. These findings reveal that cell density-regulated ferroptosis is mediated by TAZ through the regulation of EMP1-NOX4, suggesting its therapeutic potential for RCC and other TAZ-activated tumors.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

Related Links:

Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we examined the anti-tumor effect of the antibody toxin conjugate (ADC) against activated matriptase positive mantle cell lymphoma cell lines (JeKo-1, Maver, Mino, and Z138). This ADC was cytotoxic to these cell lines with IC50s between 5 and 14 μg/mL. The ADC also showed a dose dependent anti-tumor effect on the JeKo-1 xenograft in mice without toxicity. Introduction Mantle Cell Lymphoma (MCL), represents 6- percent of all lymphoma cases, and currently the survival time is 4–5 years, shorter compared to other hematologic malignancies (2–4). MCL cells express CD20, aberrant expression ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Xu ZY, Wang JP, Zhang Y, Wu SW, Ma L, Qin YZ, Wang ZP, Chai DM, Tao YS Abstract Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion renal cell carcinoma (Xp11.2 translocation RCC) was first classified as a distinct type of renal tumor by the World Health Organization in 2004. However, its morphology and clinical manifestations often overlap with those of conventional RCCs. Moreover, a micropapillary pattern (MPP) comprising small papillary cell clusters surrounded by lacunar spaces has never been described in RCC. We compared the clinicopathological and prognostic characteristics of one patient...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma. Int J Oncol. 2018 Jun 29;: Authors: Zhu J, Zhao J, Yu Z, Shrestha S, Song J, Liu W, Lan W, Xing J, Liu S, Chen C, Cao M, Sun X, Wang Q, Song X Abstract Parthenolide (PTL) is a sesquiterpene lactone compound obtained from Tanacetum parthenium (feverfew) and inhibits the activation of nuclear factor (NF)-κB. Epoxymicheliolide (EMCL) is a compound which is structurally related to PTL; however, EMCL is ...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
Xp11 translocation renal cell carcinoma (RCC) with SFPQ/PSF-TFE3 gene fusion is a rare epithelial tumor. Of note, the appearance of the gene fusion does not necessarily mean that it is renal cell carcinoma. The corresponding mesenchymal neoplasms, including Xp11 neoplasm with melanocytic differentiation, TFE3 rearrangement-associated perivascular epithelioid cell tumor (PEComa) and melanotic Xp11 translocation renal cancer, can also harbor the identical gene fusion. However, the differences between Xp11 translocation RCC and the corresponding mesenchymal neoplasm have only recently been described.
Source: Human Pathology - Category: Pathology Authors: Source Type: research
In recent years, an increasing number of TFE3 rearrangement‐associated tumors with melanotic features have been reported as primary neoplasm in different anatomical sites, including the kidney. Melanotic Xp11 translocation renal cancer (MXTRC) and Xp11 renal cell carcinoma with melanotic features (XRCCM) have been proposed to be main categories for pigmented lesions in the microophthalmia‐associated transcription factor (MiTF/TFE3) family of renal tumors that may show variable degrees of melanocytic differentiation. Herein we report a rare case of TFE3‐related pigmented renal tumor showing unusual immunoexpression of...
Source: Pathology International - Category: Pathology Authors: Tags: Case Report Source Type: research
SPOP promotes tumor progression via activation of β-catenin/TCF4 complex in clear cell renal cell carcinoma. Int J Oncol. 2016 Sep;49(3):1001-8 Authors: Zhao W, Zhou J, Deng Z, Gao Y, Cheng Y Abstract Renal cell carcinoma (RCC) is the most common type of kidney cancer, about one third of the cases are diagnosed at advanced stages with metastases and effective treatments for metastatic RCC are lacking. The molecular events supporting RCC progression remain poorly understood. SPOP, an E3 ubiquitin ligase component, was recently showed to sufficiently promote RCC tumorigenesis, however, other potent...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
This article reviews emerging entities in renal epithelial neoplasia, including tubulocystic carcinoma, clear-cell–papillary renal cell carcinoma (RCC), thyroid-like follicular RCC, ALK-related RCC, translocation RCC, acquired cystic disease–related RCC, succinate dehydrogenase–deficient RCC, and hereditary leiomyomatosis-RCC syndrome–associated RCC. Many of these rarer subtypes of RCC were recently studied in more depth and are included in the upcoming version of the World Health Organization classification of tumors.
Source: Surgical Pathology Clinics - Category: Pathology Authors: Source Type: research
Abstract Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease. Thus, distingu...
Source: Archives of Pathology and Laboratory Medicine - Category: Laboratory Medicine Authors: Tags: Arch Pathol Lab Med Source Type: research
Discussion Previous reports suggested that epithelial malignancies in allograft kidneys are rare. We identified 4 such tumors in 1584 transplant patients. Further, we identified the first reported case of translocation RCC in an allograft kidney. While the rate of malignancy in allograft kidneys is low, screening of the donor kidneys by ultrasound and/or urine cytology may be of use in detecting these lesions.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
More News: Cancer & Oncology | Carcinoma | Cytology | Epithelial Cancer | Kidney Cancer | Renal Cell Carcinoma | Translocation