SALL Proteins; Common and Antagonistic Roles in Cancer

SIMPLE SUMMARY: Transcription factors play essential roles in regulating gene expression, impacting the cell phenotype and function, and in the response of cells to environmental conditions. Alterations in transcription factors, including gene amplification or deletion, point mutations, and expression changes, are implicated in carcinogenesis, cancer progression, metastases, and resistance to cancer treatments. Not surprisingly, transcription factor activity is altered in numerous cancers, representing a unique class of cancer drug targets. This review updates and integrates information on the SALL family of transcription factors, highlighting the synergistic and/or antagonistic functions they perform in various cancer types. ABSTRACT: SALL proteins are a family of four conserved C2H2 zinc finger transcription factors that play critical roles in organogenesis during embryonic development. They regulate cell proliferation, survival, migration, and stemness; consequently, they are involved in various human genetic disorders and cancer. SALL4 is a well-recognized oncogene; however, SALL1–3 play dual roles depending on the cancer context and stage of the disease. Current reviews of SALLs have focused only on SALL2 or SALL4, lacking an integrated view of the SALL family members in cancer. Here, we update the recent advances of the SALL members in tumor development, cancer progression, and therapy, highlighting the synergistic and/or antagonistic functions they perform in similar cancer contexts. We identified common regulatory mechanisms, targets, and signaling pathways in breast, brain, liver, colon, blood, and HPV-related cancers. In addition, we discuss the potential of the SALL family members as cancer biomarkers and in the cancer cells’ response to therapies. Understanding SALL proteins’ function and relationship will open new cancer biology, clinical research, and therapy perspectives.