Effect of NELL1 on lung cancer stem‑like cell differentiation

Zhai, Yuanfen; Wei, Ran; Sha, Shuang; Lin, Chengzhao; Wang, Heyong; Jiang, Xinquan; Liu, Gentao

doi:10.3892/or.2019.6954

Cited by 10 publications

(8 citation statements)

References 45 publications

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“…Reverse transcription-quantitative (RT-q) PCR. Total RNA was purified using TRIzol ® reagent (Beyotime Institute of Biotechnology) according to a standard protocol (22). The concentration and quality of all the RNA samples were valuated using a NanoDrop 2000 spectrophotometer (Thermo Fisher Scientific, Inc.).…”

Section: Methodsmentioning

confidence: 99%

TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways

Zhao

Dai

et al. 2020

Oncol Rep

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Cancer stem cells are responsible for tumorigenesis, progression, recurrence and metastasis. Intestinal stem cells (ISCs) are regarded as the origin of intestinal neoplasia. Inflammation also serves an important role in intestinal neoplasia. To explore the molecular mechanisms underlying the inflammation-mediated induction of intestinal tumorigenesis, the present study investigated the function of tumor necrosis factor (TNF)-α in the malignant transformation of ISCs. NCM460 spheroid (NCM460s) cells with higher expression of stem cell genes, such as Oct4, Nanog, Sox2 and Lgr5, and with a higher ratio of CD133 + , were obtained from NCM460 cells in serum-free medium. TNF-α accelerated cell proliferation, migration and invasion, induced chemotherapy resistance and the epithelial-mesenchymal transition. NF-κB and Wnt/β-catenin pathways were activated in TNF-α-induced inflammatory responses, leading to the nuclear translocation of p65 and β-catenin, as well as promoter activity of NF-κB and TCF/LEF transcription factors. It was further demonstrated that TNF-α-induced activation of the NF-κB and Wnt/β-catenin signaling pathways, as well as the upregulation of proinflammatory cytokines, were significantly suppressed by p65-knockdown. Notably, PDTC, an inhibitor of NF-κB signaling, reversed TNF-α-induced activation of the NF-κB and Wnt/β-catenin pathways. A similar role was observed for IWP-2, an inhibitor of Wnt/β-catenin signaling. Collectively, these results demonstrated that the NF-κB and Wnt/β-catenin pathways were activated to promote TNF-α-induced malignant transformation of ISCs, in which these two pathways cross-regulated each other.

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Section: Methodsmentioning

confidence: 99%

TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways

Zhao

Dai

et al. 2020

Oncol Rep

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“…[72] The neural EGFL like 1 (NELL1) has also been reported to induce differentiation in stem-like cells in lung cancer through inhibiting c-MET-Notch signaling. [73] Wnt signaling pathway is another cascade with the ability to drive both tumor growth and differentiation. The canonical Wnt pathway involves stabilization of free β-catenin which upon translocation into the nucleus drives the transcription of target genes.…”

Section: Signaling Pathways With Dual Rolesmentioning

confidence: 99%

“…[ 72 ] The neural EGFL like 1 (NELL1) has also been reported to induce differentiation in stem‐like cells in lung cancer through inhibiting c‐MET‐Notch signaling. [ 73 ]…”

Section: Signaling Pathways As Potent Targets For Differentiation Therapymentioning

confidence: 99%

Critical regulatory levels in tumor differentiation: Signaling pathways, epigenetics and non‐coding transcripts

et al. 2021

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Approaches to induce tumor differentiation often result in manageable and therapynaïve cellular states in cancer cells. This transformation is achieved by activating pathways that drive tumor cells away from plasticity, a state that commonly correlates with enhanced aggression, metastasis and resistance to therapy. Here, we discuss signaling pathways, epigenetics and non-coding RNAs as three main regulatory levels with the potential to drive tumor differentiation and hence as potential targets in differentiation therapy approaches. The success of an effective therapeutic regimen in one cancer, however, does not necessarily sustain across cancer types; a phenomenon largely resulting from heterogeneity in the genetic and physiological landscapes of tumor types necessitating an approach designed for each cancer's unique genetic and phenotypic build-up.

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“…These associations of Nell-1 expression with tumor tissues make the effects of Nell-1 in tumorigenesis inconclusive. However, Nell-1 increased the chemotherapeutic sensitivity of 95-D lung cancer stem-like cells (Zhai et al 2019), had a negative effect on myoblast invasion (Rapa et al 2012), and inhibited renal cell carcinoma cell migration and adhesion (Nakamura et al 2015). These limited functional studies indicated that Nell-1 may act as a tumor suppressor candidate.…”

Section: Potential Concerns Of Nell-1 For Bone Tissue Engineering Appmentioning

confidence: 99%

Nell-1 Is a Key Functional Modulator in Osteochondrogenesis and Beyond

Zhang

Zheng

et al. 2019

J Dent Res

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Neural EGFL-like 1 (Nell-1) is a well-studied osteogenic factor that has comparable osteogenic potency with the Food and Drug Administration–approved bone morphogenic protein 2 (BMP-2). In this review, which aims to summarize the advanced Nell-1 research in the past 10 y, we start with the correlation of structural and functional relevance of the Nell-1 protein with the identification of a specific receptor of Nell-1, contactin-associated protein-like 4 (Cntnap4), for osteogenesis. The indispensable role of Nell-1 in normal craniofacial and appendicular skeletal development and growth was also defined by using the newly developed tissue-specific Nell-1 knockout mouse lines in addition to the existing transgenic mouse models. With the achievements on Nell-1’s osteogenic therapeutic evaluations from multiple preclinical animal models for local and systemic bone regeneration, the synergistic effect of Nell-1 with BMP-2 on osteogenesis, as well as the advantages of Nell-1 as an osteogenic protein with antiadipogenic, anti-inflammatory, and provascularized characteristics over BMP-2 in bone tissue engineering, is highlighted, which lays the groundwork for the clinical trial approval of Nell-1. At the molecular level, besides the mitogen-activated protein kinase (MAPK) signaling pathway, we emphasize the significant involvement of the Wnt/β-catenin pathway as well as the key regulatory molecules Runt-related transcription factor 2 (Runx2) in Nell-1-induced osteogenesis. In addition, the involvement of Nell-1 in chondrogenesis and its relevant pathologies have been revealed with the participation of the nuclear factor of activated T cells 1 (Nfatc1), Runx3, and Indian hedgehog (Ihh) signaling pathways, although the mechanistic insights of Nell-1’s osteochondrogenic property will be continuously evolving. With this perspective, we elucidate some emerging and novel functional properties of Nell-1 in oral-dental and neural tissues that will be the frontiers of future Nell-1 studies beyond the context of bone and cartilage. As such, the therapeutic potential of Nell-1 continues to evolve and grow with continuous pursuit.

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Effect of NELL1 on lung cancer stem‑like cell differentiation

Cited by 10 publications

References 45 publications

TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways

TNF‑α promotes the malignant transformation of intestinal stem cells through the NF‑κB and Wnt/β‑catenin signaling pathways

Critical regulatory levels in tumor differentiation: Signaling pathways, epigenetics and non‐coding transcripts

Nell-1 Is a Key Functional Modulator in Osteochondrogenesis and Beyond

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