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14 pages, 3062 KiB

Open AccessArticle

A Network of 17 Microtubule-Related Genes Highlights Functional Deregulations in Breast Cancer

by Sylvie Rodrigues-Ferreira, Morgane Morin, Gwenn Guichaoua, Hadia Moindjie, Maria M. Haykal, Olivier Collier, Véronique Stoven and Clara Nahmias

Cancers 2023, 15(19), 4870; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15194870 - 06 Oct 2023

Cited by 1 | Viewed by 1120

Abstract

A wide panel of microtubule-associated proteins and kinases is involved in coordinated regulation of the microtubule cytoskeleton and may thus represent valuable molecular markers contributing to major cellular pathways deregulated in cancer. We previously identified a panel of 17 microtubule-related (MT-Rel) genes that [...] Read more.

A wide panel of microtubule-associated proteins and kinases is involved in coordinated regulation of the microtubule cytoskeleton and may thus represent valuable molecular markers contributing to major cellular pathways deregulated in cancer. We previously identified a panel of 17 microtubule-related (MT-Rel) genes that are differentially expressed in breast tumors showing resistance to taxane-based chemotherapy. In the present study, we evaluated the expression, prognostic value and functional impact of these genes in breast cancer. We show that 14 MT-Rel genes (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B, KIFC1, AURKB, KIF2C, GTSE1, KIF15, KIF11, RACGAP1, STMN1) are up-regulated in breast tumors compared with adjacent normal tissue. Six of them (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B) are overexpressed by more than 10-fold in tumor samples and four of them (KIF11, AURKB, TPX2 and KIFC1) are essential for cell survival. Overexpression of all 14 genes, and underexpression of 3 other MT-Rel genes (MAST4, MAPT and MTUS1) are associated with poor breast cancer patient survival. A Systems Biology approach highlighted three major functional networks connecting the 17 MT-Rel genes and their partners, which are centered on spindle assembly, chromosome segregation and cytokinesis. Our studies identified mitotic Aurora kinases and their substrates as major targets for therapeutic approaches against breast cancer. Full article

(This article belongs to the Special Issue Microtubule-Associated Proteins (MAPs) and Cancers)

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22 pages, 4543 KiB

Open AccessArticle

Tau Regulates Glioblastoma Progression, 3D Cell Organization, Growth and Migration via the PI3K-AKT Axis

by Alessandra Pagano, Gilles Breuzard, Fabrice Parat, Aurélie Tchoghandjian, Dominique Figarella-Branger, Tiphany Coralie De Bessa, Françoise Garrouste, Alexis Douence, Pascale Barbier and Hervé Kovacic

Cancers 2021, 13(22), 5818; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225818 - 19 Nov 2021

Cited by 11 | Viewed by 3523

Abstract

The Microtubule-Associated Protein Tau is expressed in several cancers, including low-grade gliomas and glioblastomas. We have previously shown that Tau is crucial for the 2D motility of several glioblastoma cell lines, including U87-MG cells. Using an RNA interference (shRNA), we tested if Tau [...] Read more.

The Microtubule-Associated Protein Tau is expressed in several cancers, including low-grade gliomas and glioblastomas. We have previously shown that Tau is crucial for the 2D motility of several glioblastoma cell lines, including U87-MG cells. Using an RNA interference (shRNA), we tested if Tau contributed to glioblastoma in vivo tumorigenicity and analyzed its function in a 3D model of multicellular spheroids (MCS). Tau depletion significantly increased median mouse survival in an orthotopic glioblastoma xenograft model. This was accompanied by the inhibition of MCS growth and cell evasion, as well as decreased MCS compactness, implying N-cadherin mislocalization. Intracellular Signaling Array analysis revealed a defective activation of the PI3K/AKT pathway in Tau-depleted cells. Such a defect in PI3K/AKT signaling was responsible for reduced MCS growth and cell evasion, as demonstrated by the inhibition of the pathway in control MCS using LY294002 or Perifosine, which did not significantly affect Tau-depleted MCS. Finally, analysis of the glioblastoma TCGA dataset showed a positive correlation between the amount of phosphorylated Akt-Ser473 and the expression of MAPT RNA encoding Tau, underlining the relevance of our findings in glioblastoma disease. We suggest a role for Tau in glioblastoma by controlling 3D cell organization and functions via the PI3K/AKT signaling axis. Full article

(This article belongs to the Special Issue Microtubule-Associated Proteins (MAPs) and Cancers)

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Review

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33 pages, 2497 KiB

Open AccessReview

Tau Protein as Therapeutic Target for Cancer? Focus on Glioblastoma

by Rayane Hedna, Hervé Kovacic, Alessandra Pagano, Vincent Peyrot, Maxime Robin, François Devred and Gilles Breuzard

Cancers 2022, 14(21), 5386; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14215386 - 01 Nov 2022

Cited by 10 | Viewed by 3279

Abstract

Despite being extensively studied for several decades, the microtubule-associated protein Tau has not finished revealing its secrets. For long, Tau has been known for its ability to promote microtubule assembly. A less known feature of Tau is its capability to bind to cancer-related [...] Read more.

Despite being extensively studied for several decades, the microtubule-associated protein Tau has not finished revealing its secrets. For long, Tau has been known for its ability to promote microtubule assembly. A less known feature of Tau is its capability to bind to cancer-related protein kinases, suggesting a possible role of Tau in modulating microtubule-independent cellular pathways that are associated with oncogenesis. With the intention of finding new therapeutic targets for cancer, it appears essential to examine the interaction of Tau with these kinases and their consequences. This review aims at collecting the literature data supporting the relationship between Tau and cancer with a particular focus on glioblastoma tumors in which the pathological significance of Tau remains largely unexplored. We will first treat this subject from a mechanistic point of view showing the pivotal role of Tau in oncogenic processes. Then, we will discuss the involvement of Tau in dysregulating critical pathways in glioblastoma. Finally, we will outline promising strategies to target Tau protein for the therapy of glioblastoma. Full article

(This article belongs to the Special Issue Microtubule-Associated Proteins (MAPs) and Cancers)

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