MycN promotes TRPM7 expression and cell migration in neuroblastoma through a process that involves polyamines

Lange, Ingo; Koomoa, Dana-Lynn T.

doi:10.1016/j.fob.2014.10.012

Cited by 13 publications

(11 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous research has demonstrated that TRPM7 is correlated with the poor prognosis of various malignancies such as neuroblastoma ( 19 , 29 ). Thus, we performed Kaplan-Meier analysis to investigate the prognostic role of TRPM7 in bladder cancer patients.…”

Section: Discussionmentioning

confidence: 99%

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth

et al. 2017

View full text Add to dashboard Cite

Recent findings suggest that the melastatin transient receptor potential channel 7 (TRPM7) is overexpressed in many types of cancers and is involved in tumorigenesis. However, its expression pattern and the potential role in bladder cancer remain unclear. The aim of the present study was to investigate the expression status of TRPM7 and its relationship with the development of bladder cancer. In the present study, we observed that the expression of TRPM7 was significantly elevated in bladder cancer tissues compared with that noted in the adjacent non-tumor tissues. Furthermore, increased TRPM7 expression was significantly associated with recurrence, metastasis and prognosis. In addition, after knockdown of the expression of TRPM7 by siRNA, the proliferation and the motility of T24 and 5637 cells were obviously inhibited, and downregulation of TRPM7 was found to play an important role in bladder cancer cell apoptosis. In conclusion, our findings suggest that TRPM7 plays an important role in bladder cancer, and TRPM7 may serve as a potentially unfavorable factor and novel target for human bladder cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The observed effect extends to different cell lines tested of different MYCN-status however the efficiency of FTY-720 in inducing cell death seems to correlate with TRPM7 expression levels. Overexpression of MYCN, which has been reported to lead to increased levels of TRPM7 [ 24 , 25 ], slightly shifts the IC 50 value of FTY-720 to lower levels in the SHEP NB cells. FTY-720 effects were similar in IMR32 NB cells, which express high functional TRPM7 compared to MYCN non-amplified cell lines cells lines as previously reported [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of MYCN, which has been reported to lead to increased levels of TRPM7 [ 24 , 25 ], slightly shifts the IC 50 value of FTY-720 to lower levels in the SHEP NB cells. FTY-720 effects were similar in IMR32 NB cells, which express high functional TRPM7 compared to MYCN non-amplified cell lines cells lines as previously reported [ 25 ]. Strikingly, when comparing two cell lines derived from the same patient at the time of diagnosis where patient was responsive to treatment (SK-N-Be1) and after relapse and development of multi-drug resistance (SK-N-Be(2)c), the apoptosis inducing effect of FTY-720 was more potent in the drug-resistant cell line compared to the drug sensitive cell line.…”

Section: Discussionmentioning

confidence: 99%

FTY-720 induces apoptosis in neuroblastoma via multiple signaling pathways

et al. 2017

Self Cite

View full text Add to dashboard Cite

Neuroblastoma (NB) is the most common extra-cranial pediatric solid tumor. High-risk NB is difficult to treat due to the lack of response to current therapies and aggressive disease progression. Despite novel drugs, alternative treatments and multi-modal treatments, finding an effective treatment strategy for these patients continues to be a major challenge. The current study focuses on examining the effects of FTY-720 or fingolimod, a drug that is FDA-approved for refractory multiple sclerosis, in NB. The results showed that FTY-720 regulates multiple pathways that result in various effects on calcium signaling, ion channel activation and cell survival/death pathways. FTY-720 rapidly inhibits TRPM7 channel activity, and inhibited TRPM7 kinase activity, modulates calcium signaling, induces a loss of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore, and ultimately leads to cell death. Interestingly, the data also showed that low concentrations of FTY-720 sensitized drug-resistant NB cells to antineoplastic drugs. These results suggest that FTY-720 may be an attractive alternative for the treatment of NB.

show abstract

“…TRPM7 : The transient receptor potential cation channel family member and kinase TRPM7 regulates mechanical cellular interactions within microenvironments by interacting with the cellular cytoskeleton, integrating adhesion and differentiation responses with microenvironmental stimuli. TRPM7 expression is essential for maintaining NC cell multipotency, contributes to NB by disrupting NB cell maturation and preserving progenitor CSC-like features, and is promoted by N-Myc in NB cells[ 127 , 128 ]. TRPM7 expression is closely associated with NB CSC-like cell migratory and metastatic behaviour[ 129 ], controls developmental transcription through SNAI2, helping to maintain progenitor-like features[ 130 , 131 ], enhances therapeutic resistance[ 132 ] and may also promote metastasis via Hsp90a/uPA/MMP-2 signalling[ 133 ].…”

Section: Molecules and Mechanisms That Promote Select And Maintain Nb Cscsmentioning

confidence: 99%

Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting

Farina¹,

Cappabianca²,

Zelli³

et al. 2021

WJSC

View full text Add to dashboard Cite

Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumours that originate from cells of neural crest (NC) origin and in particular neuroblasts committed to the sympathoadrenal progenitor cell lineage. Therapeutic resistance, post-therapeutic relapse and subsequent metastatic NB progression are driven primarily by cancer stem cell (CSC)-like subpopulations, which through their self-renewing capacity, intermittent and slow cell cycles, drug-resistant and reversibly adaptive plastic phenotypes, represent the most important obstacle to improving therapeutic outcomes in unfavourable NBs. In this review, dedicated to NB CSCs and the prospects for their therapeutic eradication, we initiate with brief descriptions of the unique transient vertebrate embryonic NC structure and salient molecular protagonists involved NC induction, specification, epithelial to mesenchymal transition and migratory behaviour, in order to familiarise the reader with the embryonic cellular and molecular origins and background to NB. We follow this by introducing NB and the potential NC-derived stem/progenitor cell origins of NBs, before providing a comprehensive review of the salient molecules, signalling pathways, mechanisms, tumour microenvironmental and therapeutic conditions involved in promoting, selecting and maintaining NB CSC subpopulations, and that underpin their therapy-resistant, self-renewing metastatic behaviour. Finally, we review potential therapeutic strategies and future prospects for targeting and eradication of these bastions of NB therapeutic resistance, post-therapeutic relapse and metastatic progression.

show abstract

MycN promotes TRPM7 expression and cell migration in neuroblastoma through a process that involves polyamines

Cited by 13 publications

References 55 publications

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth

FTY-720 induces apoptosis in neuroblastoma via multiple signaling pathways

Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting

Contact Info

Product

Resources

About