Working model of the novel peptide or a small molecule that targets the interaction between the HDAC complex and its transcription factor recruiter, SALL4. (A) Top panel: SALL4 represses its downstream targets by recruiting an HDAC complex, NuRD, to specific promoter regions such as the PTEN promoter, resulting in histone deacetylation, a more compact chromatin structure, and transcription repression. Bottom panel: the wt peptide (or a small molecule) competes with SALL4 in interacting with NuRD. The repression of PTEN by SALL4 is therefore lost and the PTEN expression is up-regulated, leading to tumor growth inhibition. (B) In some tumor cells (such as the human endometrioid cancer line AN3CA), PTEN is deleted, so the disruption of the SALL4/HDAC complex does not affect cell growth. (C) Some tumors (such as KBM5) do not express SALL4, in which case PTEN will be regulated independently of SALL4 and the wt peptide will not have any effects on cell growth.