The new advance of SALL4 in cancer - Function, regulation, and implication

Sep 24, 2026

SALL4 (split-like protein 4) is a zinc finger transcription factor homologous to Drosophila spalt (sal) and governs embryonic stem cell self-renewal and pluripotency. During normal development, SALL4 expression decreases and becomes absent in most adult tissues, yet it is reactivated in many human cancers. Dysregulated SALL4 supports proliferation, apoptosis, metastasis, and drug resistance, acting as either epigenetic activator or repressor. It also coordinates downstream gene expression and key signaling pathways, making SALL4 a diagnostic and prognostic biomarker and therapeutic target.

LanguageEnglish

CategoryHealthcare

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Introduction

DOI: 10. 1002/jcla.24927 R E V I E W A RTI C LE The new advance of SALL4 in cancer: Function, regulation, and implication Fatma A. Abouelnazar1 | Xiaoxin Zhang1 | Maoye Wang1 | Jiahui Zhang1 | Dan Yu1 | Xueyan Zang1 | Jiayin Zhang1 | Yixin Li1 | Jing Xu1 | Qiurong Yang1 | Yue Zhou1 | Haozhou Tang1 | Yanzheng Wang1 | Jianmei Gu2 | Xu Zhang1 1Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China 2Department of Clinical Laboratory Medicine, Affiliated Cancer Hospital of Nantong University, Nantong, China Correspondence Xu Zhang, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China. [Email:](Email: xuzhang@ujs.edu.cn)[ xuzhang@ujs.edu.cn](Email: xuzhang@ujs.edu.cn) Jianmei Gu, Department of Clinical Laboratory Medicine, Affiliated Cancer Hospital of Nantong University, Nantong, China. [Email:](Email: gujianmei2010@163.com)[ gujianmei2010@163.com](Email: gujianmei2010@163.com) Funding information Key Laboratory of Molecular Diagnosticsand Precision Medicine for Surgical Oncology in Gansu Province, Grant/ Award Number: 2019GSZDSYS01 and 2019GSZDSYS02; Nantong Science and Technology Bureau Project, Grant/ Award Number: JC2021092; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, Grant/Award Number: NLDTG2020002; Postgraduate Research & Practice Innovation Program of Jiangsu Province, Grant/Award Number: KYCX21 _3405 and KYCX22 _ 3713; Priority Academic Program Development of Jiangsu Higher Education Institutions Abstract SALL4 (split-like protein 4) is a member of the mammalian homologs of the Drosophila homoeotic gene spalt (sal) and acts as a zinc finger transcription factor to govern the self-renewal and pluripotency of embryonic stem cells. SALL4 expression gradually decreases during development and is even absent in most adult tissues. However, increasing evidence suggests that SALL4 expression is restored in human cancersand its aberrant expression is associated with the progression of many hematopoietic malignancies and solid tumors. The potent roles of SALL4 in regulating cancer cell proliferation, apoptosis, metastasis, and drug resistance have been reported. SALL4 plays a dual role in epigenetic modulation by acting as either an activator or a repressor of its target genes. Furthermore, SALL4 interacts with other partners to control the expression of many downstream genes and the activation of various key signaling transduction pathways. SALL4 is considered as a promising diagnostic and prognostic biomarker and therapeutic target for cancer. In this review, we highlighted the major advances in the roles and mechanisms of SALL4 in cancer and the therapeutic strategies for targeting SALL4 to treat cancer. K E Y WO R D S biomarker, cancer, miRNA, SALL4, therapeutic target This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC. J Clin Lab Anal. 2023;37:e24927 . [https://doi.org/10.1002/jcla.24927](https://doi.org/10.1002/jcla.24927) [wileyonlinelibrary.com/journal/jcla](wileyonlinelibrary.com/journal/jcla) 1 of 16 1 | INTRODUCTION SALL4 (split-like protein 4) is identified as a member of the mammalian homologs ofthe homeotic gene spalt (sal) of Drosophila.1 Human SALL4 is located on chromosome 20.q13 .2 and has two isoforms, SALL4A, and SALL4B, due to different internal splicing in exon 2.1,2 SALL4 is composed of four zinc-finger clusters (ZFCs), three of which have a pair or a trio of C2H2-type zinc fingers, which are responsible for the DNA binding activity.1 By interacting with OCT4, SOX2, and Nanog, S

FAQs

What role does SALL4 play in embryonic stem cells?

SALL4 functions as a zinc finger transcription factor that regulates self-renewal and pluripotency by interacting with factors such as OCT4, SOX2, and Nanog.

How is SALL4 expression related to cancer development?

SALL4 expression is restored in human cancers, where abnormal expression is linked to progression of multiple hematopoietic malignancies and solid tumors.

Why is SALL4 considered a diagnostic/prognostic biomarker and therapeutic target?

SALL4 activity influences cancer cell proliferation, apoptosis, metastasis, and drug resistance, and its expression is associated with disease progression and outcomes; therefore it is considered promising for diagnosis, prognosis, and therapy targeting.

Sep 24, 2026

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