Data from Empty Spiracles Homeobox 2 Transcription Factor Functions as a Tumor Suppressor in Renal Cell Carcinoma by Targeting CADM1

<div>Abstract<p>Renal cell carcinoma (RCC), a prevalent urinary system malignancy, often metastasizes at an early stage. Characterized by a complex pathogenesis and high mortality rate, RCC poses a significant clinical challenge. We evaluated the expression level of empty spiracles homeobox 2 (<i>EMX2</i>) in patients with RCC and revealed a significant reduction of <i>EMX2</i> expression, correlating with a poor prognosis in patients with RCC. <i>EMX2</i> functions as a tumor suppressor and inhibits RCC cell proliferation and migration, accompanied by programmed cell death. Implantation of <i>EMX2</i>-transduced RCC cells beneath the mouse kidney capsule or subcutaneous injection of transduced RCC cells results in a reduction in tumor growth and size. Through RNA sequencing and chromatin immunoprecipitation sequencing analyses, we have identified cell adhesion molecule 1 (<i>CADM1</i>) as a direct transcriptional target of <i>EMX2</i>’s suppressive effects. <i>CADM1</i> induction by <i>EMX2</i> triggers PARP1-mediated parthanatos, a specific type of cell death due to mitochondrial oxidation reduction, in migrating RCC cells. Concurrently, <i>EMX2–CADM1</i> upregulation instigates caspase-3–dependent apoptosis in attached RCC cells. Furthermore, the <i>EMX2–CADM1</i> transcriptional axis also inhibits the PI3K–AKT pathway to impair RCC cell growth. Hence, the orchestrated effects mediated by the <i>EMX2–CADM1</i> axis promote RCC cell death and suppress its growth and invasion, providing potential intervention strategies for combating RCC.</p>Implications:<p>The <i>EMX2–CADM1</i> transcriptional axis offers a promising therapeutic target for inducing cell death and inhibiting growth and invasion in RCC, which could lead to more effective treatment strategies for this aggressive malignancy.</p></div>