Article
Multidisciplinary Sciences
Yang Liu, Xiangyun Li, Yue Fan, Haimin Xu, Yijin Gu, Lei Dong, Luting Zhou, Xiaoqun Yang, Chaofu Wang
Summary: This study explored the expression features of different renal entities and found that weak TFE3 expression does not indicate TFE3 rearrangement, while strong TFE3 expression is more likely to indicate TFE3-rearranged RCC. Young age combined with morphological features (psammomatous calcification and pattern multiplicity) may indicate the diagnosis of rearranged RCC.
Review
Biochemistry & Molecular Biology
Audrey Simonaggio, Damien Ambrosetti, Virginie Verkarre, Marie Auvray, Stephane Oudard, Yann-Alexandre Vano
Summary: MiTF/TFE translocation renal cell carcinoma (tRCC) is a rare and aggressive subtype of RCC, which is more prevalent in the pediatric population and represents 4% of all RCCs in adults. The diagnosis of tRCC involves translocations of genes such as TFE3, TFEB or MITF. TFE break-apart fluorescent in situ hybridization (FISH) is considered the gold standard for diagnosis. tRCC exhibits heterogeneous clinical behaviors and is more aggressive in adults. Effective treatment options for metastatic tRCC are limited, highlighting the need for better therapeutic approaches. Comprehensive genetic sequencing analyses have provided insights into the biological heterogeneity of tRCC, aiding in the development of more effective treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Xiaofan Lu, Nassim Tawanaie Pour Sedehi, Xiaoping Su, Fangrong Yan, Omar Alhalabi, Nizar M. Tannir, Gabriel G. Malouf
Summary: The prevalence of MiT family translocation renal cell carcinomas (TRCC) is higher in Asian and Black patients compared to White patients, and these tumors in Asian and Black patients have distinct transcriptional features and poor outcomes.
Review
Genetics & Heredity
Jinglong Tang, Masaya Baba
Summary: The MiT/TFE family of transcription factors, including MITF, TFEB, TFE3, and TFEC, play important roles in the development of renal cell carcinoma (RCC). The germline variant of MITF p.E318K has been identified as a risk factor for RCC. Further research on the molecular function of the MiT/TFE family is needed for better diagnosis and treatment of these rare diseases.
Review
Oncology
Payal Kapur, James Brugarolas, Kiril Trpkov
Summary: A range of renal tumors associated with TSC/mTOR pathway gene alterations have been recently described. These tumors include RCC FMS, ESC RCC, EVT, and LOT. This report summarizes recent advances and discusses their evolving complexity.
Article
Pathology
Anna Calio, Stefano Marletta, Matteo Brunelli, Serena Pedron, Sofia Canete Portillo, Diego Segala, Elena Bariani, Stefano Gobbo, George Netto, Guido Martignoni
Summary: TFE3/TFEB-rearranged renal cell carcinomas have a wide histological spectrum and require immunohistochemical markers, such as CA9, GATA3, AMACR, CK7, and parvalbumin, for accurate diagnosis.
Article
Multidisciplinary Sciences
Athena Jessica S. Ong, Cerys E. Bladen, Tara A. Tigani, Anthony P. Karamalakis, Kimberley J. Evason, Kristin K. Brown, Andrew G. Cox
Summary: The maintenance of redox and metabolic homeostasis is crucial for embryonic development. The transcription factor NRF2 plays a central role in regulating redox balance and cellular metabolism and is repressed by KEAP1 under normal conditions. In this study, we show that loss of Keap1 leads to activation of Nrf2 and postdevelopmental lethality due to severe liver abnormalities characterized by an accumulation of lysosomes. We also demonstrate that loss of Keap1 promotes aberrant activation of transcription factors TFEB and TFE3, resulting in lysosomal biogenesis. The findings highlight the importance of the KEAP1-NRF2 pathway in regulating lysosomal homeostasis during embryonic development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Jose A. Martina, David Guerrero-Gomez, Eva Gomez-Orte, Jose Antonio Barcena, Juan Cabello, Antonio Miranda-Vizuete, Rosa Puertollano
Summary: Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH-30, are regulated by a novel mechanism involving cysteine-mediated redox switch under stress conditions, leading to oligomer formation and increased stability to stress. Cysteine oxidation acts as a molecular switch linking redox balance changes with expression of target genes.
Article
Medicine, Research & Experimental
Chiara Di Malta, Angela Zampelli, Letizia Granieri, Claudia Vilardo, Rossella De Cegli, Laura Cinque, Edoardo Nusco, Salvatore Pece, Daniela Tosoni, Francesca Sanguedolce, Nicolina Cristina Sorrentino, Maria J. Merino, Deborah Nielsen, Ramaprasad Srinivasan, Mark W. Ball, Christopher J. Ricketts, Cathy D. Vocke, Martin Lang, Baktiar Karim, Luisa Lanfrancone, Laura S. Schmidt, W. Marston Linehan, Andrea Ballabio
Summary: Birt-Hogg-Dube (BHD) syndrome is a cancer syndrome characterized by the development of various tumors and caused by loss-of-function mutations in the FLCN gene. In this study, the researchers found that TFEB and TFE3, two transcription factors involved in lysosomal biogenesis and autophagy, play a role in renal cystogenesis and tumorigenesis. They also discovered that inhibiting TFEB or TFE3 could prevent tumor formation in BHD renal tumor cell line-derived xenografts. These findings suggest potential therapeutic strategies targeting TFEB and TFE3 for BHD syndrome.
EMBO MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Eutteum Jeong, Jose A. Martina, Pablo S. Contreras, Juhyung Lee, Rosa Puertollano
Summary: TFEB and TFE3 interact with the FACT complex, regulating the transcription of stress-induced genes. FACT plays a crucial role in regulating cellular homeostasis.
Article
Cell Biology
Ankur R. Sangoi, Khaleel Al-Obaidy, Liang Cheng, Chia-Sui Kao, Emily Chan, Sudha Sadasivan, Albert M. Levin, Isabel Alvarado-Cabrero, Lakshmi P. Kunju, Rohit Mehra, Rahul Mannan, Xioming Wang, Jasreman Dhillon, Maria Tretiakova, Steven C. Smith, Ondrej Hes, Sean R. Williamson
Summary: Psammomatous calcifications in clear cell renal cell carcinoma are rare and usually associated with MITF family translocation RCC. This study identified clear cell RCCs with psammomatous calcifications and found that these tumors exhibited typical features of clear cell RCC but showed negativity for specific markers, indicating they are not MITF family translocation RCC.
Article
Oncology
Daniela C. Salles, Kaushal Asrani, Juhyung Woo, Thiago Vidotto, Hans B. Liu, Igor Vidal, Andres Matoso, George J. Netto, Pedram Argani, Tamara L. Lotan
Summary: The expression of GPNMB is upregulated in tRCC and TSC1/2-associated tumors, suggesting a potential overlap in the pathogenesis and molecular markers between the two.
JOURNAL OF PATHOLOGY
(2022)
Review
Pathology
Gladell P. Paner, Vaibhav Chumbalkar, Rodolfo Montironi, Holger Moch, Mahul B. Amin
Summary: This article proposes a pragmatic approach to grading renal cell carcinoma (RCC), categorizing different subtypes into seven groups based on their clinical applicability and histological characteristics. It aims to identify the gaps in understanding and application of grading in RCC subtypes and provide guidance to surgical pathologists in terms of clinically useful grading information.
ADVANCES IN ANATOMIC PATHOLOGY
(2022)
Article
Plant Sciences
Zhenpeng Niu, Guihua Tang, Xuenan Wang, Xu Yang, Yueqin Zhao, Yinyuan Wang, Qin Liu, Fan Zhang, Yuhan Zhao, Xiao Ding, Xiaojiang Hao
Summary: This study investigated the effect of trigonochinene E (TE) on lysosomal biogenesis and autophagy, and revealed the underlying mechanisms. The results showed that TE promotes lysosomal biogenesis and autophagy by activating transcription factors TFEB and TFE3. Mechanistically, TE regulates lysosomal biogenesis and autophagy through the PERK-calcineurin axis and IRE1 alpha-STAT3 axis. Furthermore, TE-induced autophagy protects NP cells from oxidative stress to ameliorate intervertebral disc degeneration (IVDD).
Review
Cell Biology
Josue M. J. Ramirez Reyes, Rafael Cuesta, Arnim Pause
Summary: FLCN is a tumor suppressor gene responsible for BHD syndrome, and it plays a crucial role in regulating cellular metabolism through complex interactions with other proteins, particularly in lysosomal regulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
