A Proteomics Analysis Reveals 9 Up-Regulated Proteins Associated with Altered Cell Signaling in Colon Cancer Patients

Vodolazhsky, D. I.; Кутилин, Денис С.; Enin, Yaroslav S.; Gevorkyan, Yury A.; Zolotukhin, Peter; Boumber, Yanis; Kharin, Leonid; Panina, Svetlana

doi:10.1007/s10930-017-9746-6

Cited by 11 publications

(9 citation statements)

References 45 publications

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“…However, analysis of the TCGA database did not confirm the data [115]. At the protein level, increased TAU phosphorylation at Ser199/202 is a predictor of non-metastatic colon cancer [136]. Consistent with a main hypothesis for AD, hyperphosphorylated forms of TAU with impaired microtubule binding were reported in colorectal cell lines [137].…”

Section: Tau As a Prognostic Marker In Cancermentioning

confidence: 91%

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: Tau As a Prognostic Marker In Cancermentioning

confidence: 91%

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

Papin

Paganetti

2020

Brain Sciences

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“…However, these data are not confirmed by analyzing the TCGA database [96]. At the protein level, increased TAU phosphorylation at Ser199/202 is a predictor of nonmetastatic colon cancer [121]. Consistent with a main hypothesis for AD, hyperphosphorylated forms of TAU with impaired microtubule binding were reported in colorectal cell lines [122].…”

Section: Tau and Cancermentioning

confidence: 85%

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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“…Hyperphosphorylated tau has been detected in prostate and colon cancer cell lines. Additionally, increased levels of phospho-tau were shown to be a marker for nonmetastatic colon cancer [ 79 , 80 , 81 ].…”

Section: The Contribution Of Ck1 To the Modulation Of Cytoskeleton Co...mentioning

confidence: 99%

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

Roth

Gihring

Bischof

et al. 2022

Cancers

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Protein kinases of the Casein Kinase 1 family play a vital role in the regulation of numerous cellular processes. Apart from functions associated with regulation of proliferation, differentiation, or apoptosis, localization of several Casein Kinase 1 isoforms to the centrosome and microtubule asters also implicates regulatory functions in microtubule dynamic processes. Being localized to the spindle apparatus during mitosis Casein Kinase 1 directly modulates microtubule dynamics by phosphorylation of tubulin isoforms. Additionally, site-specific phosphorylation of microtubule-associated proteins can be related to the maintenance of genomic stability but also microtubule stabilization/destabilization, e.g., by hyper-phosphorylation of microtubule-associated protein 1A and RITA1. Consequently, approaches interfering with Casein Kinase 1-mediated microtubule-specific functions might be exploited as therapeutic strategies for the treatment of cancer. Currently pursued strategies include the development of Casein Kinase 1 isoform-specific small molecule inhibitors and therapeutically useful peptides specifically inhibiting kinase-substrate interactions.

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A Proteomics Analysis Reveals 9 Up-Regulated Proteins Associated with Altered Cell Signaling in Colon Cancer Patients

Cited by 11 publications

References 45 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

Tau: At the Interface Between Neurodegeneration and Cancer?

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

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