Special Issue "FAK Signaling Pathway in Cancers"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 May 2018)

Special Issue Editors

Guest Editor
Dr. Philippe Rondé

Laboratoire de Biophotonique et Pharmacologie, CNRS, UMR 7213, Illkirch, France; Université de Strasbourg, Faculté de Pharmacie, Illkirch, France
Website | E-Mail
Interests: migration; invasion; focal adhesion; FAK; melanoma
Guest Editor
Dr. Laurence Choulier

UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral Signaling and Therapeutic Targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch, France
Website | E-Mail
Interests: nucleic acid aptamer; cell-surface biomarkers; integrin; glioblastoma

Special Issue Information

Dear Colleagues,

More than twenty-five years ago, Focal Adhesion Kinase (FAK) was described as a substrate of the oncogene product of the Rous sarcoma virus, v-Src, and as a protein, highly phosphorylated upon clustering of integrins at focal adhesions. Consequently, FAK was shown to be primarily implicated in the regulation of signals initiated at sites of integrin-mediated cell adhesion, as well as signals triggered upon growth factor receptors activation.

Subsequent studies revealed that FAK plays fundamental roles in cell survival, growth, motility, and invasion. Thus, FAK is involved in many aspects of the metastatic process, as well as overexpression, hyperphosphorylation, and/or elevated activity of FAK, have been reported in a variety of human cancers, including sarcomas and carcinomas associated with tumor growth, neoangiogenesis and metastatic dissemination. In addition to its localization at focal adhesions, FAK was recently found in unexpected places, including endosomes and adherent junctions. The new role for nuclear FAK has also been recognized and new insights were made on the mechanism of FAK dimerization and its role in FAK activity.

The development of FAK antagonists, as anti-cancer therapy, led to several small inhibitors of FAK kinase function that are currently undergoing clinical trials. In addition to its kinase function, FAK possesses scaffolding functions that are highly relevant in cancer signalling. New and recent investigations also showed that FAK antagonists may display therapeutic benefits in cancer patients by acting on the immune system, triggering T-cells-mediated immune response. FAK antagonists may also be used to reduce cancer resistance, notably when associated with BRAF inhibitors in melanoma patients.

This Special Issue will highlight the current state-of-the-art in FAK biology and future prospects for improving therapies.

Dr. Philippe Rondé
Dr. Laurence Choulier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

View options order results:
result details:
Displaying articles 1-3
Export citation of selected articles as:

Review

Open AccessReview Targeting Focal Adhesion Kinase Using Inhibitors of Protein-Protein Interactions
Cancers 2018, 10(9), 278; https://doi.org/10.3390/cancers10090278
Received: 18 July 2018 / Revised: 8 August 2018 / Accepted: 14 August 2018 / Published: 21 August 2018
Cited by 1 | PDF Full-text (1507 KB) | HTML Full-text | XML Full-text
Abstract
Focal adhesion kinase (FAK) is a cytoplasmic non-receptor protein tyrosine kinase that is overexpressed and activated in many human cancers. FAK transmits signals to a wide range of targets through both kinase-dependant and independent mechanism thereby playing essential roles in cell survival, proliferation, [...] Read more.
Focal adhesion kinase (FAK) is a cytoplasmic non-receptor protein tyrosine kinase that is overexpressed and activated in many human cancers. FAK transmits signals to a wide range of targets through both kinase-dependant and independent mechanism thereby playing essential roles in cell survival, proliferation, migration and invasion. In the past years, small molecules that inhibit FAK kinase function have been developed and show reduced cancer progression and metastasis in several preclinical models. Clinical trials have been conducted and these molecules display limited adverse effect in patients. FAK contain multiple functional domains and thus exhibit both important scaffolding functions. In this review, we describe the major FAK interactions relevant in cancer signalling and discuss how such knowledge provide rational for the development of Protein-Protein Interactions (PPI) inhibitors. Full article
(This article belongs to the Special Issue FAK Signaling Pathway in Cancers)
Figures

Figure 1

Open AccessReview Dynamics of p14ARF and Focal Adhesion Kinase-Mediated Autophagy in Cancer
Cancers 2018, 10(7), 221; https://doi.org/10.3390/cancers10070221
Received: 3 June 2018 / Revised: 22 June 2018 / Accepted: 26 June 2018 / Published: 29 June 2018
Cited by 2 | PDF Full-text (1650 KB) | HTML Full-text | XML Full-text
Abstract
It has been widely shown that the focal adhesion kinase (FAK) is involved in nearly every aspect of cancer, from invasion to metastasis to epithelial–mesenchymal transition and maintenance of cancer stem cells. FAK has been shown to interact with p14ARF (alternative reading frame)—a [...] Read more.
It has been widely shown that the focal adhesion kinase (FAK) is involved in nearly every aspect of cancer, from invasion to metastasis to epithelial–mesenchymal transition and maintenance of cancer stem cells. FAK has been shown to interact with p14ARF (alternative reading frame)—a well-established tumor suppressor—and functions in the negative regulation of cancer through both p53-dependent and -independent pathways. Interestingly, both FAK and ARF (human and mouse counterpart) proteins, as well as p53, are involved in autophagy—a process of “self-digestion”—whose main function is the recycling of cellular components and quality control of proteins and organelles. In the last years, an unexpected role of p14ARF in the survival of cancer cells has been underlined in different cellular contexts, suggesting a novel pro-oncogenic function of this protein. In this review, the mechanisms whereby ARF and FAK control autophagy are presented, as well as the role of autophagy in cell migration and spreading. Integrated investigation of these cell functions is extremely important to understand the mechanism of the basis of cell transformation and migration and thus cancer development. Full article
(This article belongs to the Special Issue FAK Signaling Pathway in Cancers)
Figures

Figure 1

Open AccessReview Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development
Cancers 2018, 10(6), 196; https://doi.org/10.3390/cancers10060196
Received: 7 May 2018 / Revised: 31 May 2018 / Accepted: 6 June 2018 / Published: 11 June 2018
Cited by 3 | PDF Full-text (2302 KB) | HTML Full-text | XML Full-text
Abstract
Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 have been found to have promising antitumor activity, their clinical long-term [...] Read more.
Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 have been found to have promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled via modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved in this control are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and with particular focus on how these mechanisms could inspire or improve anticancer therapies. Full article
(This article belongs to the Special Issue FAK Signaling Pathway in Cancers)
Figures

Figure 1

Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top