Role of ferritinophagy in cystine deprivation-induced cell death in glioblastoma cells

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

Download Full-text

Role of WWOX WOX1 in Alzheimer s disease pathology and in cell death signaling

Frontiers in Bioscience ◽

10.2741/s358 ◽

2013 ◽

Vol S5 (1) ◽

pp. 72-85 ◽

Cited By ~ 2

Author(s):

Chih-Chung Teng

Keyword(s):

Cell Death ◽

Cell Death Signaling

Download Full-text

Faculty Opinions recommendation of New Arabidopsis thaliana cytochrome c partners: a look into the elusive role of cytochrome c in programmed cell death in plants.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718104360.793488383 ◽

2013 ◽

Author(s):

Daniel Gallie

Keyword(s):

Arabidopsis Thaliana ◽

Cell Death ◽

Cytochrome C ◽

Programmed Cell Death

Download Full-text

Faculty Opinions recommendation of The role of iron and reactive oxygen species in cell death.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718209906.793489284 ◽

2014 ◽

Author(s):

Kate Carroll ◽

Prakash Palde

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Reactive Oxygen ◽

Oxygen Species

Download Full-text

Faculty Opinions recommendation of Role of Atg5-dependent cell death in the embryonic development of Bax/Bak double-knockout mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727681479.793532876 ◽

2017 ◽

Author(s):

Sharad Kumar ◽

Donna Denton

Keyword(s):

Cell Death ◽

Embryonic Development ◽

Knockout Mice ◽

Double Knockout ◽

Dependent Cell

Download Full-text

The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

Current Medicinal Chemistry ◽

10.2174/0929867327666200128105459 ◽

2020 ◽

Vol 27 ◽

Cited By ~ 1

Author(s):

Lifang Zhang ◽

Yu Zhao ◽

Quanmei Tu ◽

Xiangyang Xue ◽

Xueqiong Zhu ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Immune Escape ◽

Hypoxia Inducible Factor ◽

Hpv Infection ◽

Advanced Cervical Cancer ◽

Cervical Carcinogenesis ◽

Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

Download Full-text