In contrast, in the absence of RASSF1A, RNF4 reduces its affinity with HES1, which remains stable regardless of upstream Notch signals or the use of Notch inhibitors [126], indicating that Notch signaling blockade at the receptor level (e.g., with γ-secretase inhibitors) may be fruitful only in the presence of RASSF1A in several cancer types, including prostate. Here, HES1 is linked to cancer.