Cyclin-dependent kinase 5 acts as a promising biomarker in clear cell Renal Cell Carcinoma

Zhu, Liangsong; Ding, Rong; Zhang, Jianping; Zhang, Jin; Lin, Zongming

doi:10.1186/s12885-019-5905-9

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…Notably, PPAR-alpha has been identified as a possible therapeutic target for the treatment of clear cell renal cell carcinoma (ccRCC) 28 , a cancer type that is molecularly and morphologically similar to OCCC 29 and one in which CDK5 signaling has also been identified as an important regulatory pathway 29 . The activation of oxidative phosphorylation in HGSOC vs OCCC cancers is consistent with previous reports of the dependency of HGSOC tumor cells on this mode of energy metabolism 30 . We further compared the protein alteration quantified here with a protein signature previously reported to stratify HGSOC and OCCC 31 , 32 , and 18 co-quantified proteins were found to exhibit concordant protein abundances ( R = 0.802, P = 0.0001) (Fig.…”

Section: Resultssupporting

confidence: 91%

Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies

et al. 2020

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Cancer has no borders: Generation and analysis of molecular data across multiple centers worldwide is necessary to gain statistically significant clinical insights for the benefit of patients. Here we conceived and standardized a proteotype data generation and analysis workflow enabling distributed data generation and evaluated the quantitative data generated across laboratories of the international Cancer Moonshot consortium. Using harmonized mass spectrometry (MS) instrument platforms and standardized data acquisition procedures, we demonstrate robust, sensitive, and reproducible data generation across eleven international sites on seven consecutive days in a 24/7 operation mode. The data presented from the high-resolution MS1-based quantitative data-independent acquisition (HRMS1-DIA) workflow shows that coordinated proteotype data acquisition is feasible from clinical specimens using such standardized strategies. This work paves the way for the distributed multi-omic digitization of large clinical specimen cohorts across multiple sites as a prerequisite for turning molecular precision medicine into reality.

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Section: Resultssupporting

confidence: 91%

Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies

et al. 2020

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“…The serine/threonine kinase CDK5, is unique among the CDK family members in that it displays no cell cycle or mitotic function since for CDK5 no classical mediators of cell-cycle transition are known [ 174 ]. Its importance in cancer development and progression [ 175 ] is suggested by the positive correlation between high CDK5 expression and poor prognosis in pancreatic [ 176 ], lung [ 177 ], and thyroid cancer [ 178 ]. In liver carcinoma cells high CDK5 expression favors angiogenesis though hypoxia-inducible factor 1 alpha (HIF-1alpha) stabilization [ 179 , 180 ], and facilitating prostate cancer cell migration [ 181 ].…”

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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“…The serine/threonine cyclin-dependent kinase 5 (CDK5), is unique among the CDK family members in that it displays no cell cycle or mitotic function since for CDK5 no classical mediators of cell-cycle transition are known [134]. Its importance in cancer development and progression [135] is suggested by the positive correlation between high CDK5 expression and poor prognosis in pancreatic [136], lung [137], and thyroid cancer [138]. In liver carcinoma cells high CDK5 expression favors angiogenesis though HIF-1alpha stabilization [139,140], and facilitating prostate cancer cell migration [141].…”

Section: The Interaction Of Tau With Proteins Linked To Cancermentioning

confidence: 99%

Tau: At the Interface Between Neurodegeneration and Cancer?

Papin¹,

Paganetti²

2020

Preprint

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For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

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Cyclin-dependent kinase 5 acts as a promising biomarker in clear cell Renal Cell Carcinoma

Cited by 11 publications

References 24 publications

Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies

Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies

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

Tau: At the Interface Between Neurodegeneration and Cancer?

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