Cancer stem cells (CSCs) are crucial regulators of tumor recurrence/progression. The maintenance of CSCs is dependent on aberrant activation of various pathways, including Hedgehog. Prevalent sialylations contribute to aggressiveness in CSCs. Here, we have addressed the role of sialylation in regulating stemness-like properties of pancreatic cancer sphere-forming cells (PCS) through modulation of the Hedgehog (Hh) pathway. The status of CD133/CD44/surface-sialylation was checked by flow cytometry and effects of Neu2 overexpression in PCS were compared using qPCR, immunoblotting, co-immunoprecipitation and also by colony-formation assays. The work was also validated in a xenograft model after Neu2 overexpression. Neu2 and Shh status in patient tissues were examined by immunohistochemistry. PCS showed higher Hh-pathway activity and sialylation with reduced cytosolic-sialidase (Neu2). Neu2 overexpression caused desialylation of Shh, thereby reducing Shh-Patched1 binding thus causing decreased Hh-pathway activity with lower expression of Snail/Slug/CyclinD1 leading to reduction of stemness-like properties. Neu2-overexpression also induced apoptosis in PCS. Additionally, Neu2-overexpressed PCS demonstrated lower mTORC2 formation and inhibitory-phosphorylation of Gsk3β, reflecting a close relationship with reduced Hh pathway. Moreover, both Neu2 and Rictor (a major component of mTORC2) co-transfection reduced stem cell markers and Hh-pathway activity in PCS. Neu2-overexpressed tumors showed reduction in tumor mass with downregulation of stem cell markers/Shh/mTOR and upregulation of Bax/Caspase8/Caspase3. Thus, we established that reduced sialylation by Neu2 overexpression leads to decreased stemness-like properties by desialylation of Shh, which impaired its association with Patched1 thereby inhibiting the Hh pathway. All these may be responsible for enhanced apoptosis in Neu2-overexpressed PCS.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349614 | PMC |
| http://dx.doi.org/10.3390/cells9061512 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integrated single-cell transcriptomic analyses identify a novel lineage plasticity-related cancer cell type involved in prostate cancer progression.
EBioMedicine
November 2024
School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:
Background: Cancer cell plasticity is the ability of neoplastic cells to alter their identity and acquire new biological properties under microenvironmental pressures. In prostate cancer (PCa), lineage plasticity often results in therapy resistance and trans-differentiation to neuroendocrine (NE) lineage. However, identifying the cancer cells harboring lineage plasticity-related status remains challenging.
View Article and Find Full Text PDFThe critical role of glutamine and fatty acids in the metabolic reprogramming of -resistant melanoma cells.
Front Pharmacol
August 2024
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
Circulating tumor cells (CTCs) represent the sub-population of cells shed into the vasculature and able to survive in the bloodstream, adhere to target vascular endothelial cells, and re-growth into the distant organ. CTCs have been found in the blood of most solid tumor-bearing patients and are used as a diagnostic marker. Although a complex genotypic and phenotypic signature characterizes CTCs, the ability to survive in suspension constitutes the most critical property, known as resistance to , e.
View Article and Find Full Text PDFWTAP/IGF2BP3-mediated GBE1 expression accelerates the proliferation and enhances stemness in pancreatic cancer cells via upregulating c-Myc.
Cell Mol Biol Lett
July 2024
Zhejiang Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Background: Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism.
View Article and Find Full Text PDFThe Human Soluble NKG2D Ligand Differentially Impacts Tumorigenicity and Progression in Temporal and Model-Dependent Modes.
Biomedicines
January 2024
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
NKG2D is an activating receptor expressed by all human NK cells and CD8 T cells. Harnessing the NKG2D/NKG2D ligand axis has emerged as a viable avenue for cancer immunotherapy. However, there is a long-standing controversy over whether soluble NKG2D ligands are immunosuppressive or immunostimulatory, originating from conflicting data generated from different scopes of pre-clinical investigations.
View Article and Find Full Text PDFm6A modified BACE1-AS contributes to liver metastasis and stemness-like properties in colorectal cancer through TUFT1 dependent activation of Wnt signaling.
J Exp Clin Cancer Res
November 2023
Health Science Center, Ningbo University, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, P. R. China.
Background: Liver metastasis is one of the most important reasons for high mortality of colorectal cancer (CRC). Growing evidence illustrates that lncRNAs play a critical role in CRC liver metastasis. Here we described a novel function and mechanisms of BACE1-AS promoting CRC liver metastasis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!