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SALL Proteins; Common and Antagonistic Roles in Cancer
Claudia Álvarez1, Aracelly Quiroz1, Diego Benítez-Riquelme1
1Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 3349001, Chile.
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.
Insights
The SALL protein family, including SALL1-4, plays crucial roles in organogenesis and cancer. This review integrates their functions in tumor development and therapy, offering new perspectives for cancer research.
Area of Science:
- Molecular Biology
- Developmental Biology
- Oncology
Background:
- SALL proteins are transcription factors vital for embryonic development.
- They regulate cell proliferation, survival, migration, and stemness.
- Dysregulation of SALL proteins is linked to genetic disorders and cancer.
Purpose of the Study:
- To provide an integrated review of all SALL family members (SALL1-4) in cancer.
- To highlight their roles in tumor development, progression, and therapeutic response.
- To identify common regulatory mechanisms and signaling pathways across various cancers.
Main Methods:
- Literature review and synthesis of recent advances on SALL proteins in cancer.
- Analysis of SALL protein functions in diverse cancer types including breast, brain, liver, colon, blood, and HPV-related cancers.
- Identification of common regulatory mechanisms, targets, and signaling pathways.
Main Results:
- SALL4 is a known oncogene, while SALL1-3 exhibit context-dependent dual roles in cancer.
- Synergistic and antagonistic functions of SALL proteins were observed in similar cancer contexts.
- Common regulatory mechanisms, targets, and pathways were identified across multiple cancer types.
- Potential of SALL proteins as cancer biomarkers and in modulating therapy response was discussed.
Conclusions:
- An integrated understanding of the SALL family is crucial for advancing cancer biology.
- SALL proteins offer potential as biomarkers and therapeutic targets.
- Further research into SALL protein functions can open new avenues for cancer treatment and clinical research.
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