The role of Capon in multiple myeloma

Shen, Yun; Liu, Haiyan; Gu, Shengqing; Wei, Ziwei; Liu, Hong

doi:10.1177/1010428317713674

Cited by 4 publications

(4 citation statements)

References 24 publications

(27 reference statements)

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“…Other TAU interacting proteins with strong relevance for cancer are the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein CAPON [225], the probable ATP-dependent DEAD-Box RNA helicase DDX6 [226], the proto-oncogene tyrosine-protein kinase SRC [227], the tyrosine-protein kinase ABL1 [228], the dual specificity tyrosine-phosphorylation-regulated kinase 1A DYRK1A [229], the EWS RNA-binding protein 1 (EWSR1) [230] and the sirtuin family [231].…”

Section: Protein-protein Interactions Linking Tau To Cancermentioning

confidence: 99%

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Papin

Paganetti

2020

Brain Sciences

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Neurodegenerative disorders and cancer may appear unrelated illnesses. Yet, epidemiologic studies indicate an inverse correlation between their respective incidences for specific cancers. Possibly explaining these findings, increasing evidence indicates that common molecular pathways are involved, often in opposite manner, in the pathogenesis of both disease families. Genetic mutations in the MAPT gene encoding for TAU protein cause an inherited form of frontotemporal dementia, a neurodegenerative disorder, but also increase the risk of developing cancer. Assigning TAU at the interface between cancer and neurodegenerative disorders, two major aging-linked disease families, offers a possible clue for the epidemiological observation inversely correlating these human illnesses. In addition, the expression level of TAU is recognized as a prognostic marker for cancer, as well as a modifier of cancer resistance to chemotherapy. Because of its microtubule-binding properties, TAU may interfere with the mechanism of action of taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network and impair cell division. Indeed, a low TAU expression is associated to a better response to taxanes. Although TAU main binding partners are microtubules, TAU is able to relocate to subcellular sites devoid of microtubules and is also able to bind to cancer-linked proteins, suggesting a role of TAU in modulating microtubule-independent cellular pathways associated to oncogenesis. This concept is strengthened by experimental evidence linking TAU to P53 signaling, DNA stability and protection, processes that protect against cancer. This review aims at collecting literature data supporting the association between TAU and cancer. We will first summarize the evidence linking neurodegenerative disorders and cancer, then published data supporting a role of TAU as a modifier of the efficacy of chemotherapies and of the oncogenic process. We will finish by addressing from a mechanistic point of view the role of TAU in de-regulating critical cancer pathways, including the interaction of TAU with cancer-associated proteins.

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Section: Protein-protein Interactions Linking Tau To Cancermentioning

confidence: 99%

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Papin

Paganetti

2020

Brain Sciences

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“…Silencing CAPON enhanced anchorage- independent growth in breast cancer cells 18. In addition, interference with CAPON expression promoted the proliferation of multiple myeloma cells 19. We previously reported that overexpression of CAPON-S inhibited cell proliferation and decreased the activity of AKT signaling in U87 cells 20.…”

Section: Introductionmentioning

confidence: 93%

Effects of Long Form of CAPON Overexpression on Glioma Cell Proliferation are Dependent on AKT/mTOR/P53 Signaling

et al. 2019

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Background: CAPON has two isoforms in human brain: long form of CAPON (CAPON-L) and short form of CAPON (CAPON-S). Recent studies have indicated the involvement of CAPON in tumor cell growth. We aimed to reveal the role of the two CAPON isoforms in the proliferation of glioma cells in this study. Materials and Methods: Lentivirus-mediated stable cell lines with CAPON-L or CAPON-S overexpression were established in U87 and U251 glioma cells. Cell counting kit-8 and colony formation assays were used to evaluate cell proliferation. Western blot analysis of cell cycle-related proteins and flow cytometry were performed to analyze cell cycle progression. Some important molecules of the AKT/mTOR pathway and P53 were also measured by Western blot analysis. Results: Overexpression of CAPON-L showed a significantly inhibitory role in U251 cells, while it exhibited a promoting role in U87 cells. Consistently, overexpressing CAPON-L impeded the cell cycle progression and down-regulated the expression levels of Cyclin D1, CDK4 and CDK6 in U251 cells, whereas it up-regulated the CDK6 level in U87 cells. The overexpression of CAPON-L significantly decreased the phosphorylation and/or total levels of AKT, mTOR and S6 in U251 cells, while it did not affect these signaling molecules in U87 cells, except for a significant increase in the phosphorylation of AKT at Thr-308 site. Transfecting constitutively active AKT (myr-AKT) partially reversed the decreased phosphorylation of AKT and S6 in the CAPON-L-overexpressing U251 cells. In addition, we found a significant decrease in the wild-type P53 level in the CAPON-L-overexpressing U87 cells. The overexpression of CAPON-S also inhibited cell proliferation, blocked cell cycle progression, and decreased the AKT/mTOR pathway activity in U251 cells. Conclusion: The effects of CAPON-L overexpression on glioma cell proliferation are dependent on the AKT/mTOR/P53 activity. The overexpression of CAPON inhibits U251 cell proliferation through the AKT/mTOR signaling pathway, while overexpressing CAPON-L promoted U87 cell proliferation, possibly through down-regulating the P53 level.

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“…However, this effect is not present in U87 cells, while overexpression of CAPON-S inhibits Akt signaling in U87 cells [112]. Shen et al found that CAPON overexpression was associated with myeloma cell adhesion, cell growth, and cell-adhesion-mediated drug resistance [113]. A decrease in CAPON expression level not only induces the expression of Akt and p-Akt, but also increases cell adhesion and shortens the cellular G1 cycle.…”

Section: Capon Affects Tumor Growthmentioning

confidence: 99%

“…Acute brain injury [27,97,98] Acute spinal cord injury [99] Neurodegenerative diseases Alzheimer's disease [25,57] Huntington's disease [117,118] Parkinson's disease [100] Amyotrophic lateral sclerosis [101] Major depressive disorder [102,107] Bipolar disorder [102] Anxiety disorders [33,103,107] Post-traumatic stress disorder [104,105] Schizophrenia Schizophrenia [40,110,111] Cerebrovascular disease Ischemic stroke [27,99] Skeletal muscle disease Duchenne muscular dystrophy [36,116] Cancer Glioma [67,112] Myeloma [112,113] Breast cancer [67,114]…”

Section: Dendritic Development Of Neurons In the Brainmentioning

confidence: 99%

The Physiological Function of nNOS-Associated CAPON Proteins and the Roles of CAPON in Diseases

Xie,

Xing,

et al. 2023

IJMS

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In this review, the structure, isoform, and physiological role of the carboxy-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) are summarized. There are three isoforms of CAPON in humans, including long CAPON protein (CAPON-L), short CAPON protein (CAPON-S), and CAPON-S’ protein. CAPON-L includes three functional regions: a C-terminal PDZ-binding motif, carboxypeptidase (CPE)-binding region, and N-terminal phosphotyrosine (PTB) structural domain. Both CAPON-S and CAPON-S’ only contain the C-terminal PDZ-binding motif. The C-terminal PDZ-binding motif of CAPON can bind with neuronal nitric oxide synthase (nNOS) and participates in regulating NO production and neuronal development. An overview is given on the relationship between CAPON and heart diseases, diabetes, psychiatric disorders, and tumors. This review will clarify future research directions on the signal pathways related to CAPON, which will be helpful for studying the regulatory mechanism of CAPON. CAPON may be used as a drug target, which will provide new ideas and solutions for treating human diseases.

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The role of Capon in multiple myeloma

Cited by 4 publications

References 24 publications

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Effects of Long Form of CAPON Overexpression on Glioma Cell Proliferation are Dependent on AKT/mTOR/P53 Signaling

The Physiological Function of nNOS-Associated CAPON Proteins and the Roles of CAPON in Diseases

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