Year: 2026
Type: preprint
Abstract: Summary Xp11.2 translocation RCC [Xp11.2 tRCC]) is an underdiagnosed and aggressive subtype of RCC with few specific or targeted therapies. The transmembrane glycoprotein CD44 is an emerging target in many advanced malignancies, and with its ligand OPN ( SPP1 ), is a crucial driver of cancer progression, stemness, metastasis, and immune suppression. Here we show that common TFE3 -fusions [including SFPQ-TFE3, PRCC-TFE3, ASPSCR1-TFE3 , and NONO-TFE3 ] are associated with upregulated expression of CD44 and SPP1, as observed in multiple human and murine bulk transcriptomic studies and a murine tRCC snRNA-Seq dataset. CD44 and/or SPP1 protein expression were also upregulated in murine models of transgenic tRCC kidneys and urine specimens, patient-derived cell lines and human tRCC cases, by immunoblotting and/or IHC. Transient deletion of CD44 was associated with profound and specific suppression of tRCC cell line growth, with decreased mTOR signaling. These data suggest that CD44 and/or SPP1 may potentially drive tumorigenesis in tRCC.
Authors: Kaushal Asrani, Juhyung Woo, Thiago Vidotto, Kewen Feng, Alan Lorenzetti, Eddie Imada, Huili Li, Rajan Singh, Anand Thotakura, Sangeeta Ray, Lia Oliveira, Adrianna Amaral, Vikrant Palande, Ravi Anchoori, Jayaprakash Mandal, Roy Elias, Christopher Thoburn, Md. Masud Rana, Hrishikesh Gangule, Alexander Gao, Pornima Phatak, James Donahue, Yasser Ged, Nirmish Singla, John Copland, Laura Schmidt, W. Marston Linehan, Pedram Argani, Tamara Lotan
Institutions: Johns Hopkins University, Johns Hopkins Medicine, All India Institute of Medical Sciences, University of Alabama at Birmingham, Birmingham VA Medical Center, Mayo Clinic in Florida, National Institutes of Health, National Cancer Institute, Center for Cancer Research, Frederick National Laboratory for Cancer Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7213986262