ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK–AKT–mTOR Signaling Pathway

Nguyen, Khoa; Yan, Yuanqing; Yuan, Bin; Dasgupta, Abhishek; Sun, Jerry Chih‐Yuan; Mu, Hong; Anh, Kim; Ueno, Naoto T.; Andreeff, Michael; Battula, V. Lokesh

doi:10.1158/1535-7163.mct-18-0399

Cited by 70 publications

(68 citation statements)

References 44 publications

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“…EZR-negative tumor cells also show the significant upregulation of CD109 , ID4 , ST8SIA1 , and NR4A1 genes. In breast cancer, CD109, ID4, and ST8SIA1 are involved in the maintenance of stem cell phenotype [ 44 , 45 , 46 ], whereas NR4A1 promotes TGF-β-induced EMT and invasion [ 47 ]. Besides, these genes are associated with RFS of breast cancer patients according to Kaplan–Meier plotter [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

Gerashchenko

Zolotaryova

Kiselev

et al. 2020

Cancers

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Intratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data were used to identify genes differentially expressed between solid, trabecular, and other morphological arrangements of tumor cells. Immunohistochemistry was applied to evaluate the association of the selected proteins with metastasis. RNA-sequencing was performed to analyze the molecular makeup of metastatic tumor cells. High frequency of metastases and decreased metastasis-free survival were detected in patients either with positive expression of KIF14 or Mieap or negative expression of EZR at the tips of the torpedo-like structures in breast cancers. KIF14- and Mieap-positive and EZR-negative cells were mainly detected in the torpedo-like structures of the same breast tumors; however, their transcriptomic features differed. KIF14-positive cells showed a significant upregulation of genes involved in ether lipid metabolism. Mieap-positive cells were enriched in genes involved in mitophagy. EZR-negative cells displayed upregulated genes associated with phagocytosis and the chemokine-mediated signaling pathway. In conclusion, the positive expression of KIF14 and Mieap and negative expression of EZR at the tips of the torpedo-like structures are associated with breast cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

Gerashchenko

Zolotaryova

Kiselev

et al. 2020

Cancers

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“…Proliferating, neural stem cells express both GD3 as well as measurable levels of GD2 [ 70 ]. Interaction of GD3 with the EGF receptor was found to allow neural stem cells to continue to proliferate [ 71 ] while studies of breast cancer stem-like cells indicated that activation of the FAK-AKT-ERK-mTOR signaling pathway by GD2 enhanced cell proliferation ( Table 3 ) [ 72 ]. These observations support the hypothesis that GD3 and GD2 contribute to the undifferentiated state of neural stem cells (NSCs) and in NB that GD2 contributes to the oncogenic properties.…”

Section: Gangliosides In Neuroblastomamentioning

confidence: 99%

Gangliosides and Neuroblastomas

Schengrund

2020

IJMS

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The focus of this review is the ganglio-series of glycosphingolipids found in neuroblastoma (NB) and the myriad of unanswered questions associated with their possible role(s) in this cancer. NB is one of the more common solid malignancies of children. Five-year survival for those diagnosed with low risk NB is 90–95%, while that for children with high-risk NB is around 40–50%. Much of the survival rate reflects age of diagnosis with children under a year having a much better prognosis than those over two. Identification of expression of GD2 on the surface of most NB cells led to studies of the effectiveness and subsequent approval of anti-GD2 antibodies as a treatment modality. Despite much success, a subset of patients, possibly those whose tumors fail to express concentrations of gangliosides such as GD1b and GT1b found in tumors from patients with a good prognosis, have tumors refractory to treatment. These observations support discussion of what is known about control of ganglioside synthesis, and their actual functions in NB, as well as their possible relationship to treatment response.

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“…Overexpression of GD2 in tumors may occur as a consequence of aberrant expression of GD2 biosynthetic enzymes. For example, ST8SIA1 regulated GD2 expression and breast CSC function [40,57]. Overexpression of ST8SIA1 in MDA‐MB‐231 breast cancer cells increased GD2 at the cell surface and enhanced proliferation of the cells.…”

Section: Biological Roles Of Gd2 In Cancermentioning

confidence: 99%

Targeting glycosphingolipids for cancer immunotherapy

Hung

Wang

et al. 2020

FEBS Letters

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Aberrant expression of glycosphingolipids (GSLs) is a unique feature of cancer and stromal cells in tumor microenvironments. Although the impact of GSLs on tumor progression remains largely unclear, anticancer immunotherapies directed against GSLs are attracting growing attention. Here, we focus on GD2, a disialoganglioside expressed in tumors of neuroectodermal origin, and Globo H ceramide (GHCer), the most prevalent cancer-associated GSL overexpressed in a variety of epithelial cancers. We first summarize recent advances on our understanding of GD2 and GHCer biology and then discuss the clinical development of the first immunotherapeutic agent targeting a glycolipid, the GD2-specific antibody dinutuximab, its approved indications, and new strategies to improve its efficacy for neuroblastoma. Next, we review ongoing clinical trials on Globo H-targeted immunotherapeutics. We end with highlighting how these studies provide sound scientific rationales for targeting GSLs in cancer and may facilitate a rational design of new GSL-targeted anticancer therapeutics.

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ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK–AKT–mTOR Signaling Pathway

Cited by 70 publications

References 44 publications

The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

Gangliosides and Neuroblastomas

Targeting glycosphingolipids for cancer immunotherapy

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