Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway

Zhu, Bowen; Wu, Yanqin; Niu, Lizhi; Wang, Yao; Xue, Mengzhou; Wang, Hongyu; Yang, Jun; Li, Jiaping; Fan, Wenzhe

doi:10.3389/fonc.2020.574383

Cited by 7 publications

(10 citation statements)

References 47 publications

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“…The transition from high expression levels of E-cadherin to low expression levels of N-cadherin are trademarks of aggressive tumor growth and stimulates initiation of the EMT, a key process during the initiation of tumor metastasis. Zhu et al additionally identified SAPCD2 overexpression being significantly correlated with metastasis in fibrosarcoma patients and demonstrated that SAPCD2 knockdown attenuated lung metastasis in vivo by activating the Hippo signaling pathway as described above [33]. Together, the above reports illustrate the ability of SAPCD2 to influence the main metastatic signaling cascades.…”

Section: The Role Of Sapcd2 In Tumor Metastasis and The Underlying Me...mentioning

confidence: 70%

“…The expression of SAPCD2 in fibrosarcoma was demonstrated for the first time by Zhu et al [33]. Fibrosarcoma is a highly malignant cancer of mesenchymal origin with a high potential to metastasize to the lung.…”

Section: Sapcd2 In Other Cancer Typesmentioning

confidence: 96%

“…Fibrosarcoma is a highly malignant cancer of mesenchymal origin with a high potential to metastasize to the lung. Interested in the relevance of SAPCD2 in fibrosarcoma and lung metastasis, Zhu et al utilized both retrospective clinical investigations and in vitro experiments to investigate the role of SAPCD2 in aggravating fibrosarcoma [33]. Kaplan-Meier analysis revealed that fibrosarcoma patients exhibiting a higher expression level of SAPCD2 are correlated with worse overall survival.…”

Section: Sapcd2 In Other Cancer Typesmentioning

confidence: 99%

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The Function and Regulation of SAPCD2 in Physiological and Oncogenic Processes

Baker¹,

Du²

2022

J. Cancer

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The Suppressor APC Domain Containing 2 (SAPCD2) gene, also known by its aliases p42.3 and c9orf140, encodes a protein with an approximate molecular weight of 42.3 kDa. It was initially recognized as a cell cycle-associated protein involved in mitotic progression. Since the initial discovery of this gene, emerging evidence has suggested that its functions extend beyond that of regulating cell cycle progression to include modulation of planar polarization of cell progenitors and determination of cell fate throughout embryonic development. The underlying mechanisms driving such functions have been partially elucidated. However, the detailed mechanisms of action remain to be further characterized. The expression level of SAPCD2 is high throughout embryogenesis but is generally absent in healthy postnatal tissues, with restored expression in adult tissues being associated with various disease states. The pathological consequences of its aberrant expression have been investigated, most notably in the development of several types of cancers. The role of SAPCD2 in tumorigenesis has been supported by in vitro, in vivo, and retrospective clinical investigations and the mechanisms underlying its oncogenic function have been partially revealed. The potential of SAPCD2 as a diagnostic marker and therapeutic target of cancers have also been explored and have shown great promise. However, many questions pertaining to its oncogenic mechanisms as well as its value as a diagnostic marker and therapeutic target remain to be answered. In addition to its function as an oncogene, an involvement of SAPCD2 in other pathological processes such as inflammation has also been implicated and provides additional directions that warrant future investigation. This article reviews the current understanding of the normal cellular functions of SAPCD2 and the relevance of SAPCD2 in disease development with a primary focus on tumorigenesis. The mechanisms that regulate p43.2 expression, including the potential role of microRNAs in regulating its expression, are also reviewed. To the best of our knowledge, we are the first to comprehensively review the published findings regarding the physiological and pathological functions of this gene.

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Section: The Role Of Sapcd2 In Tumor Metastasis and The Underlying Me...mentioning

confidence: 70%

Section: Sapcd2 In Other Cancer Typesmentioning

confidence: 96%

Section: Sapcd2 In Other Cancer Typesmentioning

confidence: 99%

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The Function and Regulation of SAPCD2 in Physiological and Oncogenic Processes

Baker¹,

Du²

2022

J. Cancer

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“…For the first time, we showed that oncogenes like FAM83D, SAPCD2 were downregulated upon curcumin treatment in all three cells, and TSGs like ZNF292, 77 NKAPL, and CCL21 were upregulated in breast cancer cell lines. FAM83D 78–80 and SAPCD2 81 are known to promote tumorigenesis, induce drug resistance and promote invasiveness. FAM83D promotes cell proliferation and motility by downregulating TSG FBXW7 48 .…”

Section: Discussionmentioning

confidence: 99%

Curcumin alters distinct molecular pathways in breast cancer subtypes revealed by integrated miRNA/mRNA expression analysis

2022

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Background Curcumin is well known for its anticancer properties. Its cytotoxic activity has been documented in several cancer cell lines, including breast cancer. The pleiotropic activity of curcumin as an antioxidant, an antiangiogenic, antiproliferative, and pro‐apoptotic, is due to its diverse targets, such as signaling pathways, protein/enzyme, or noncoding gene. Aim This study aimed to identify key miRNAs and mRNAs induced by curcumin in breast cancer cells MCF7, T47D (hormone positive), versus MDA‐MB231 (hormone negative) using comparative analysis of global gene expression profiles. Methods RNA was isolated and subjected to mRNA and miRNA library sequencing to study the global gene expression profile of curcumin‐treated breast cancer cells. The differential expression of gene and miRNA was performed using the DESeq R package. The enriched pathways were studied using cluster profileR, and integrated miRNA–mRNA analysis was carried out using miRtarvis and miRmapper tools. Results Curcumin treatment led to upregulation of 59% TSGs in MCF7, 21% in MDA‐MB‐231 cells, and 36% TSGs in T47D, and downregulation of 57% oncogenes in MCF7, 76% in MDA‐MB‐231, and 91% in T47D. Similarly, curcumin treatment led to upregulation of 32% TSmiRs in MCF7, 37.5% in MDA‐MB231, and 62.5% in T47D, and downregulation of 77% oncomiRs in MCF7, 50% in MDA‐MB231 and 28.6% in T47D. Integrated analysis of miRNA–mRNA led to the identification of a common NFKB pathway altered by curcumin in all three cell lines. Analysis of uniquely enriched pathway revealed non‐integrin membrane–ECM interactions and laminin interactions in MCF7; extracellular matrix organization and degradation in MDA‐MB‐231 and cell cycle arrest and G2/M transition in T47D. Conclusion Curcumin regulates miRNA and mRNA in a cell type‐specific manner. The integrative analysis led to the detection of miRNAs and mRNAs pairs, which can be used as biomarkers associated with carcinogenesis, diagnostic, and treatment response in breast cancer.

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“…Accumulating studies have shown an elevated expression level of SAPCD2 in a number of human cancers, such as colorectal cancer, fibrosarcoma, melanoma, and non-small cell lung cancer. SAPCD2 largely functions as an oncogene playing important roles in tumorigenesis by promoting cell proliferation, cell migration, and invasion by various pathways, such as PI3K/Akt activation, MAPK activation, or Hippo signaling suppression [ 10 – 13 ]. A recent study, however, suggested that SAPCD2 blocks Wnt/β-catenin signaling by interaction with Axin1 and in some contexts might function as a tumor suppressor [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7

Zhang

Cao

et al. 2022

Cell Death Dis

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Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.

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Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway

Cited by 7 publications

References 47 publications

The Function and Regulation of SAPCD2 in Physiological and Oncogenic Processes

The Function and Regulation of SAPCD2 in Physiological and Oncogenic Processes

Curcumin alters distinct molecular pathways in breast cancer subtypes revealed by integrated miRNA/mRNA expression analysis

SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7

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