The Involvement of CSRP1 in Neuroblastoma Differentiation and Apoptosis Impacting Tumor‐Suppressive Therapeutic Responses
Journal
The FASEB Journal
Journal Volume
39
Journal Issue
7
ISSN
0892-6638
1530-6860
Date Issued
2025-04-08
Author(s)
Lin, Yu‐Han
Jiang, Jyun‐Hong
Chuang, Hui‐Ching
Huang, Chao‐Cheng
Wu, Min‐Tsui
Chen, Ting‐Ya
Lian, Wei‐Shiung
Chuang, Jiin‐Haur
Abstract
Neuroblastoma (NB) is a pediatric malignancy from the neural crest, where differentiation plays a key role in prognosis. We investigated cysteine and glycine-rich protein 1 (CSRP1) as a therapeutic target for NB, as it has been linked to differentiation and carcinogenesis in various cancers. Immunohistochemical analysis of archived NB samples showed a significant correlation between CSRP1 expression and differentiation. Ectopic CSRP1 expression in MYCN-amplified BE(2)-M17 cells increased sensitivity to cisplatin, promoted neurite extension, and enhanced differentiation, apoptosis, and chemosensitivity to 13cisRA. Synergistic apoptotic effects were observed with 5-aza-2'-deoxycytidine (DAC) and Poly(I:C) treatments in SK-N-AS cells implanted in xenografts, linked to upregulation of CSRP1, innate immune receptor RIG-I, and caspase-9 activation. CSRP1 expression was significantly higher in mitochondrial DNA-depleted SK-N-AS ρ0 cells, compared to parent SK-N-AS cells. Cisplatin increased CSRP1 expression further in parent cells but not in ρ0 cells. Simultaneous upregulation of caspase-8 was found in both cell types, but increased caspase-9 only in parent cells, suggesting that both intrinsic and extrinsic apoptosis pathways are involved in CSRP1 function depending on the existence of mitochondrial DNA. These findings indicate that CSRP1 is involved in differentiation, determination of apoptosis, and possibly innate immunity in NB, which endows CSRP1 with the potential to enhance the effects of 13cisRA, DAC, and Poly(I:C) in combination therapies for NB.ABSTRACT
Subjects
CSRP1
CSRP1‐targeted therapies
apoptosis
mitochondrial integrity
neuroblastoma
xenograft
SDGs
Publisher
Wiley
Type
journal article