Role of CSN5/JAB1 in Wnt/β‐catenin activation in colorectal cancer cells

Schütz, Anke K.; Hennes, Thomas; Jumpertz, Sandra; Fuchs, Sebastian W.; Bernhagen, Jürgen

doi:10.1016/j.febslet.2012.04.037

Cited by 31 publications

(27 citation statements)

References 56 publications

(74 reference statements)

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“…COPS5 is also involved in ubiquitination and degradation of tumor‐inhibiting factors including P53 and Smad4/7 . Limited studies available indicated that COPS5 could participate in cell proliferation, invasiveness and poor prognosis of CRC . In our study, overexpression of COPS5 has been confirmed in both CRC tissues and cell lines.…”

Section: Discussionsupporting

confidence: 70%

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COPS5 and LASP1 synergistically interact to downregulate 14‐3‐3σ expression and promote colorectal cancer progression via activating PI3K/AKT pathway

Zhou

Shao

Liu

et al. 2017

Intl Journal of Cancer

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Overexpression of LIM and SH3 protein 1 (LASP1) is required for colorectal cancer (CRC) development and progression. Here, C-Jun activation domain-binding protein-1 (Jab1), also known as COP9 signalosome subunit 5 (COPS5), was verified as a new LASP1-interacting protein through yeast two-hybrid assay. The role of COPS5 in LASP1-mediated CRC progression remains unknown. GST pull-down assay indicated that the SH3 domain of LASP1 could directly bind to MPN domain of COPS5. In vitro gain- and loss-of-function analyses revealed the stimulatory role of COPS5 on CRC cell proliferation, migration and invasion. Endogenous overexpression of COPS5 could also enhance the homing capacity of CRC cells in vivo. Further analysis showed that COPS5 and LASP1 synergistically interact to stimulate the ubiquitination and degradation of 14-3-3σ and promote colorectal cancer progression via PI3K/Akt dependent signaling pathway. Clinically, the expression of COPS5 was studied in CRC tissues and it is associated with CRC differentiation, metastasis and poor prognosis. The colocalization of LASP1 and COPS5 was demonstrated in both nonmetastatic and metastatic CRC tissues. A positive correlation was found between the expression of LASP1 and COPS5 while a negative correlation existed between 14-3-3σ and COPS5/LASP1 in most CRC samples. A combination of COPS5 and LASP1 tends to be an independent prognostic indicator for CRC patients, and this is also suitable for CRC without lymph node metastasis. The current research has further advanced our understanding on the complicated molecular mechanism underlying LASP1-mediated CRC progression, which hopefully will contribute to the development of novel diagnostic and therapeutic strategies in CRC.

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Section: Discussionsupporting

confidence: 70%

“…Besides PI3K/Akt signaling pathway, we also detected the activation of MAPK signal pathway in COPS5‐overexpressed CRC cells. Moreover, Wnt/β‐catenin signal pathway was also verified participated in COPS5 stimulated CRC cell progression …”

Section: Discussionmentioning

confidence: 92%

COPS5 and LASP1 synergistically interact to downregulate 14‐3‐3σ expression and promote colorectal cancer progression via activating PI3K/AKT pathway

Zhou

Shao

Liu

et al. 2017

Intl Journal of Cancer

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“…COPS5 knockdown reduces ␤-catenin levels (35), and multimodal interactions between APP, presenilin 1 (PS1), and ␤-catenin have been reported (36), suggesting that the COPS5-␤-catenin pathway might also contribute to AD pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

COPS5 (Jab1) Protein Increases β Site Processing of Amyloid Precursor Protein and Amyloid β Peptide Generation by Stabilizing RanBP9 Protein Levels

Wang

Dey

Carrera

et al. 2013

Journal of Biological Chemistry

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Background: Increased generation of toxic amyloid ␤ peptide (A␤) in the brain is central to the pathogenesis of Alzheimer's disease (AD). Results: COPS5 (Jab1) is a novel RanBP9-interacting protein that robustly increases A␤ generation Conclusion: COPS5 increases A␤ generation by stabilizing RanBP9 protein levels. Significance: Lowering COPS5 levels may be an effective therapeutic approach for AD.

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“…Jab1 serves an intriguing function in the tumorigenic process and increased levels of Jab1 are associated with lymph node metastasis and poor prognosis of several types of human cancer, including LSCC. Jab1 may represent a prognostic indicator of malignant transformation and assists in explaining the biological behavior of a number of cancer cells, including human colorectal cancer cell lines (22) and liver cancer cells (23). It has been reported that Jab1 acts as a negative regulatory factor of p27 protein and has an association with cell proliferation in LSCC (24).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Jab1 expression inhibits proliferation and promotes apoptosis of AMC-HN-8 cells

Wang

Pan

et al. 2018

Oncol Lett

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Abstract. c-Jun activation domain-binding protein-1 (Jab1) is a multifunctional protein involved in cell proliferation and apoptosis, DNA damage and repair and genome stability. In a number of types of human carcinoma, the abnormal expression of Jab1 is associated with poor prognosis, suggesting that Jab1 serves a vital function in tumorigenesis. However, the functional effects and the underlying molecular mechanisms of Jab1 in laryngeal squamous cell carcinoma (LSCC) progression remain poorly understood. The results of the present study demonstrate that downregulating Jab1 expression promotes LSCC apoptosis while inhibiting the proliferation of LSCC cells. Furthermore, Jab1 inhibition results in decreased protein kinase B phosphorylation accompanied by increased caspase-3 cleavage and p53 expression. It has been identified that the increased expression of Jab1 is markedly associated with LSCC progression, therefore Jab1 may be used as a novel target for the treatment of laryngeal cancer.

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Role of CSN5/JAB1 in Wnt/β‐catenin activation in colorectal cancer cells

Cited by 31 publications

References 56 publications

COPS5 and LASP1 synergistically interact to downregulate 14‐3‐3σ expression and promote colorectal cancer progression via activating PI3K/AKT pathway

COPS5 and LASP1 synergistically interact to downregulate 14‐3‐3σ expression and promote colorectal cancer progression via activating PI3K/AKT pathway

COPS5 (Jab1) Protein Increases β Site Processing of Amyloid Precursor Protein and Amyloid β Peptide Generation by Stabilizing RanBP9 Protein Levels

Suppression of Jab1 expression inhibits proliferation and promotes apoptosis of AMC-HN-8 cells

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