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FEAT, the protein encoded by methyltransferase‐like 13 (METTL13), is aberrantly upregulated in most human cancers and potently drives tumorigenesis in vivo; however, its role in normal tissues remains elusive. Immunoblotting has displayed weak FEAT expression in normal human tissues, including the testis. Here, we found that FEAT is expressed in fetal and adult Leydig cells in the testis. FEAT knockdown using siRNA increased primary cilia formation in MA‐10 Leydig tumor cells, accompanied by enhanced 5′ adenosine monophosphate‐activated protein kinase (AMPK) activation. Immunofluorescence analyses of FEAT‐silenced MA‐10 cells showed diminished insulin‐like factor 3 (INSL3) expression. A male Mettl13+/− mouse developed bilateral intraabdominal cryptorchidism, suggesting defective INSL3 production by fetal Leydig cells. Leydig cells from the mouse showed markedly decreased INSL3 protein by immunohistochemistry. Together, these results suggest that FEAT facilitates the INSL3 production in testicular Leydig cells that is essential for transabdominal testis migration. FEAT (METTL13) is expressed in fetal and adult Leydig cells in the testis. FEAT‐silenced MA‐10 Leydig cells showed diminished INSL3 protein. A male Mettl13+/− mouse exhibited bilateral intraabdominal cryptorchidism and markedly decreased INSL3 expression in Leydig cells. [ABSTRACT FROM AUTHOR]

The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements. In this review, we attempt to systematically summarize results that have been gleaned from detailed in vivo characterizations of these mutants. Our goal is to describe the physiological roles of Hippo signaling in several normal organ systems, as well as to emphasize how disruption of the Hippo pathway, and particularly hyperactivation of YAP1/ TAZ, can be oncogenic. [ABSTRACT FROM AUTHOR]