SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts

Sun, Jun; Shin, Dong Yeon; Eiseman, Mark; Yallowitz, Alisha R.; Li, Na; Lalani, Sarfaraz; Li, Zan; Cung, Michelle; Bok, Seoyeon; Debnath, Shawon; Marquez, Sofia Jenia; White, Tommy E.; Khan, Abdul Ghafoor; Lorenz, Ivo C.; Shim, Jae-Hyuck; Lee, Francis S.; Xu, Ren; Greenblatt, Matthew B.

doi:10.1038/s41467-021-24819-w

Cited by 22 publications

(26 citation statements)

References 37 publications

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“…Notably, SLITRK5, an integral membrane protein, was remarkably downregulated in melanoma patients with high MUC21 expression, when compared to the low MUC21 group. Compelling study has provided evidence that SLITRK5 served a negative regulator of hedgehog signaling, which was a highly conserved evolutionary pathway and activated in several tumor types(Pasca di Magliano & Hebrok, 2003; Sun et al, 2021). Hence, we supposed that MUC21 might suppressed SLITRK5 to regulate hedgehog signaling pathway, resulting in the development of melanoma cells.…”

Section: Resultsmentioning

confidence: 99%

MUC21 controls melanoma progression via regulating SLITRK5 and hedgehog signaling pathway

Liu

Xiao

Xiong

et al. 2022

Cell Biology International

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Mucins are heavily glycosylated proteins secreted by various cell types, to protect the epithelial surface of the gastrointestinal tract from damage. Currently, increasing studies provided evidence to suggest that mucins play an essential role in regulating tumor progression. However, the role of mucins and the underpinning mechanism of how mucins drive melanoma progression remains elusive. In this study, we first demonstrated that mucin 21 (MUC21) expression was significantly upregulated in metastatic melanoma tissues, and a higher MUC21 expression resulted in poor overall survival in melanoma patients by The Cancer Genome Atlas database analysis. In vitro, MUC21 overexpression markedly promoted proliferative properties and aggressive behavior of melanoma cell A375 and A875, as assessed by Cell Counting Kit-8 and transwell assay. In mechanism, we proved that MUC21 suppressed expression of SLITRK5, an integral membrane protein, leading to activation of prosurvival hedgehog pathway and sustained melanoma development.More importantly, we found that combination of hedgehog pathway inhibitor cyclopamine and chemotherapy revealed an improved anticancer effect in MUC21 overexpression xenograft model. Altogether, our study described a novel role of MUC21 in regulating tumor progression, which offers a promising target for melanoma diagnosis and therapy.

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Section: Resultsmentioning

confidence: 99%

MUC21 controls melanoma progression via regulating SLITRK5 and hedgehog signaling pathway

Liu

Xiao

Xiong

et al. 2022

Cell Biology International

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“…In the absence of Shh protein, Ptch binds to Smo to inhibit Smo activity. In the presence of Shh, the binding of Ptch1 to Shh protein eliminates the inhibitory effect on Smo, and Smo transmits signals to downstream Gli (glioma-associated oncogene homologue) transcription factors through a complex transduction process, activating Gli and allowing transport of Gli into the nucleus ( Sun et al, 2021 ). After activated Gli enters the nucleus, it initiates the transcriptional expression of downstream Cyclin D1 and N-myc genes ( Sigafoos et al, 2021 ).…”

Section: The Molecular Regulation Of Hair Follicle Morphogenesis and ...mentioning

confidence: 99%

Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles

Lin

Liang

2022

Front. Cell Dev. Biol.

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As one of the main appendages of skin, hair follicles play an important role in the process of skin regeneration. Hair follicle is a tiny organ formed by the interaction between epidermis and dermis, which has complex and fine structure and periodic growth characteristics. The hair growth cycle is divided into three continuous stages, growth (anagen), apoptosis-driven regression (catagen) and relative quiescence (telogen). And The Morphogenesis and cycle of hair follicles are regulated by a variety of signal pathways. When the signal molecules in the pathways are abnormal, it will affect the development and cycle of hair follicles, which will lead to hair follicle-related diseases.This article will review the structure, development, cycle and molecular regulation of hair follicles, in order to provide new ideas for solving diseases and forming functional hair follicle.

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“…Additionally, SliTrk5 is selectively expressed in osteoblasts and as a negative regulator of hedgehog signal which is necessary for bone formation in osteoblasts. In vitro culture, deletion of SliTrk5 leads to an increase in hedgehog signal, but its overexpression in osteoblasts inhibits downstream targets of hedgehog signal, thus modulating osteoblast differentiation [ 57 ]. In a word, SliTrk5 is an emerging protein that is not well understood by people.…”

Section: Role Of Slitrk5 In the Development Of Cnsmentioning

confidence: 99%

The Role of SliTrk5 in Central Nervous System

Liu

Zhang

Mei

et al. 2022

BioMed Research International

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SLIT and NTRK-like protein-5 (SliTrk5) is one of the six members of SliTrk protein family, which is widely expressed in the central nervous system (CNS), regulating and participating in many essential steps of central nervous system development, including axon and dendritic growth, neuron differentiation, and synaptogenesis. SliTrk5, as a neuron transmembrane protein, contains two important conservative domains consisting of leucine repeats (LRRs) located at the amino terminal in the extracellular region and tyrosine residues (Tyr) located at the carboxyl terminal in the intracellular domains. These special structures make SliTrk5 play an important role in the pathological process of the CNS. A large number of studies have shown that SliTrk5 may be involved in the pathogenesis of CNS diseases, such as obsessive-compulsive-disorder (OCD), attention deficit/hyperactivity disorder (ADHD), glioma, autism spectrum disorders (ASDs), and Parkinson’s disease (PD). Targeting SliTrk5 is expected to become a new target for the treatment of CNS diseases, promoting the functional recovery of CNS. The purpose of this article is to review the current research progression of the role of SliTrk5 in CNS and its potential mechanisms in CNS diseases.

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SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts

Cited by 22 publications

References 37 publications

MUC21 controls melanoma progression via regulating SLITRK5 and hedgehog signaling pathway

MUC21 controls melanoma progression via regulating SLITRK5 and hedgehog signaling pathway

Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles

The Role of SliTrk5 in Central Nervous System

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