SPEN and neoplasm: However, SHARP does not exclusively regulate XCI and the Notch signaling pathway; in fact, it regulates the estrogen receptor α (ERα)-dependent transcription and mutations of SHARP have been detected in breast cancer, where it acts as a tumor suppressor [226] Similarly, SHARP expression is upregulated in colorectal adenocarcinoma, where it is described to deregulate the Wnt signaling pathway [227].