Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis

Nicolè, Lorenzo; Sanavia, Tiziana; Veronese, Nicola; Cappellesso, Rocco; Luchini, Claudio; Dabrilli, P.; Fassina, Ambrogio

doi:10.18632/oncotarget.14952

Cited by 29 publications

(27 citation statements)

References 60 publications

(43 reference statements)

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“…In this study, we reported that SALL4 expression was strikingly upregulated in NPC tissues compared with noncancerous nasopharyngeal tissues (nasal polyp), and NPC patients in T3‐4 classification often showed higher expression of SALL4. Our results were consistent with previous studies on the expression of SALL4 in other types of cancers . Additionally, studies also indicated that radiotherapy alone could successfully control less T3‐4 tumors than T1‐2 tumors, meaning T3‐4 tumors might be more resistant to radiotherapy .…”

Section: Discussionsupporting

confidence: 92%

SALL4 induces radioresistance in nasopharyngeal carcinoma via the ATM/Chk2/p53 pathway

Nie

Guo

et al. 2019

Cancer Medicine

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Radiotherapy is the mainstay and primary curative treatment modality in nasopharyngeal carcinoma (NPC), whose efficacy is limited by the development of intrinsic and acquired radioresistance. Thus, deciphering new molecular targets and pathways is essential for enhancing the radiosensitivity of NPC. SALL4 is a vital factor in the development and prognosis of various cancers, but its role in radioresistance remains elusive. This study aimed to explore the association of SALL4 expression with radioresistance of NPC. It was revealed that SALL4 expression was closely correlated with advanced T classification of NPC patients. Inhibition of SALL4 reduced proliferation and sensitized cells to radiation both in vitro and in vivo. Furthermore, SALL4 silencing increased radiation‐induced DNA damage, apoptosis, and G2/M arrest in CNE2 and CNE2R cells. Moreover, knockdown of SALL4 impaired the expression of p‐ATM, p‐Chk2, p‐p53, and anti‐apoptosis protein Bcl‐2, while pro‐apoptosis protein was upregulated. These findings indicate that SALL4 could induce radioresistance via ATM/Chk2/p53 pathway and its downstream proteins related to apoptosis. Targeting SALL4 might be a promising approach for the development of novel radiosensitizing therapeutic agents for radioresistant NPC patients.

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Section: Discussionsupporting

confidence: 92%

SALL4 induces radioresistance in nasopharyngeal carcinoma via the ATM/Chk2/p53 pathway

Nie

Guo

et al. 2019

Cancer Medicine

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“…Previously, CSCs in RCC have been identified by using either stem cell markers [CD133, CD44, CXCR4, CD105 and Spalt-Like Transcription Factor 4 (SALL4)] [ 9 – 13 ] or functional assays (sphere-forming ability, side population and ALDH activity) [ 14 – 16 ]. Especially, in RCC cell lines, ALDH high cells showed CSC properties in vitro, such as clonogenic and self-renewal ability and increased expression of OCT4 and NANOG [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma

et al. 2017

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BackgroundRenal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment.MethodsOncoLnc was used as a tool for interactively exploring survival correlations. Gene manipulation and expression analysis were carried out using siRNA, RT-PCR and Western blotting. Wound healing and invasion assays were used for phenotypical characterization. Aldefluor assay and FACS sorting Sphere culture were used to determine the “stemness” of CSCs. Co-Immunoprecipitation (Co-IP) was used to examine the interaction between OCT4 and CBFA2T2. Student’s t-test and Chi square test was used to analyze statistical significance.ResultsCBFA2T2 expression can significantly predict the survival of RCC patients. Knocking-down of CBFA2T2 can inhibit cell migration and invasion in RCC cells in vitro, and reduce ALDHhigh CSCs populations. CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines.ConclusionsOur data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.Electronic supplementary materialThe online version of this article (10.1186/s12935-017-0473-z) contains supplementary material, which is available to authorized users.

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“…Studies have utilized RNA interference methods or peptides against SALL4 to effectively inhibit tumor growth in cell culture and xenotransplant models (8)(9)(10), and drugs that can be used to target SALL4 specifically in cancer patients are being developed. However, as in all targeted therapies, SALL4centered treatment is limited to patients with tumors that are SALL4 positive, which represent only a sub-set of all cancer patients (11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

“…Targeting SALL4 by RNA interference or peptides has been shown to be effective against a wide range of cancers, including lung cancer (7), endometrial cancer (8), gastric cancer (9), and liver cancer (10). However, the fact that SALL4 is only positive in a sub-set of cancer patients limits the application of SALL4-based cancer treatment (11)(12)(13), which is broadly true for all targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Induction of a SALL4-dependency for targeted cancer therapy

Yang¹,

Gao²,

Liu³

et al. 2020

Preprint

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Oncofetal protein SALL4 is critical for tumor cell survival, making it a promising target in cancer therapy. However, it is detectable only in a subset of cancer patients, which limits the therapeutic impact of a SALL4 targeted therapy. Here we report that SALL4 can be activated and/or upregulated pharmacologically by hypomethylating agents, such as 5-Aza-2’-deoxycytidine (DAC), which are used clinically, and that SALL4 negative cancer cells become SALL4 dependent following exogenous expression of SALL4. In addition, the histone deacetylase inhibitor Entinostat (ENT) negatively regulates SALL4 expression by upregulating miR-205. Both ENT and miR-205 treatment induced cell apoptosis, rescuable by SALL4 expression or miR-205 inhibition. Finally, DAC pre-treatment sensitizes SALL4 negative cancer cell lines to ENT both in culture and in vivo by upregulating SALL4. Overall, we propose a framework whereby the scope of targeted therapy can be expanded by sensitizing cancer cells to treatment by target induction and engineered dependency.SignificanceThis proof of concept study demonstrates that targeted cancer therapy can be achieved by inducing a targetable gene establishing a survival-dependency for cancer cells. For SALL4, sequential treatment of DAC and ENT could expand the scope of SALL4 targeted cancer therapy.

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Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis

Cited by 29 publications

References 60 publications

SALL4 induces radioresistance in nasopharyngeal carcinoma via the ATM/Chk2/p53 pathway

SALL4 induces radioresistance in nasopharyngeal carcinoma via the ATM/Chk2/p53 pathway

CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma

Induction of a SALL4-dependency for targeted cancer therapy

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