SALL4, a novel marker for human gastric carcinogenesis and metastasis

Abstract

SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein levels in human gastric cancer tissues, and SALL4 level was highly correlated with lymph node metastasis. Enforced expression of SALL4 enhanced the proliferation and migration of human gastric cancer cells, whereas knockdown of SALL4 by siRNA led to the opposite effects. In addition, SALL4 overexpression promoted the growth and metastasis of gastric xenograft tumor in vivo. SALL4 overexpression induced epithelial-mesenchymal transition (EMT) in gastric cancer cells, with increased expression of Twist1, N-cadherin and decreased expression of E-cadherin. Moreover, SALL4 promoted the acquirement of stemness in gastric cancer cells through the induction of Bmi-1 and Lin28B. Taken together, our findings indicate that SALL4 has oncogenic roles in gastric cancer through the modulation of EMT and cell stemness, suggesting SALL4 as a novel target for human gastric cancer diagnosis and therapy.

High cytoplasmic expression of SALL4 predicts a malignant phenotype and poor prognosis of breast invasive ductal carcinoma

“…The staining of SALL4 was mainly found in the cytoplasm with a diffuse distribution in the nucleus. The result of predominantly cytoplasmic staining of SALL4 was dissimilar with most studies of SALL4 in other carcinomas which observed largely nuclear staining of SALL4 [15,29,30]. Under some circumstances, some kinds of transcription factors may be located in the cytoplasm prior to activation, and become relocated in the nucleus in response to the appropriate signal [31].…”

“…SALL4, as a specific and sensitive marker, has been proved to be beneficial in screening out metastatic germ cell tumors, especially metastatic yolk sac tumors [11]. SALL4 was demonstrated to play an oncogenic role in gastric cancer by modulating cell stemness and epithelial-mesenchymal transition and supposed to be a new target for diagnosis and therapy for human gastric cancer [15]. The over expression of SALL4 has been observed in human liver cancer [28].…”

“…SALL4B transgenic mice developed myelodysplastic syndrome (MDS) -like features and subsequently acute myeloid leukemia [10]. Consecutively, the expression of SALL4 has been recorded in varied kinds of cancers and is deemed to have a clinical value for diagnosis in a few of them, including germ cell tumor, aggressive hepatocellular carcinoma, colorectal cancer, gastric cancer and extragonadal yolk sac tumors [11][12][13][14][15]. However, the information on expression and prognostic value of SALL4 in breast cancer was quite limited [16,17].…”

SALL4: An emerging cancer biomarker and target

“…In contrast, down-regulation of SALL4 inhibits liver cancer cell proliferation in vitro as well as in tumor xenograft models. We have recently reported that SALL4-overexpression enhances while knockdown of SALL4 inhibits the proliferation of gastric cancer cells [34]. In consistent with this observation, SALL4 knockdown also inhibits endometrial cancer cell growth in vitro and tumorigenicity in vivo due to the inhibition of cell proliferation and increased apoptosis [35].…”

“…The research from our group has indicated that the SALL4 level is highly correlated with lymph node metastasis of gastric cancer [34]. Enforced expression of SALL4 enhances the migration of human gastric cancer cells, whereas knockdown of SALL4 by siRNA leads to the opposite effects.…”