Special Issue "Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis"

Quicklinks

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

Deadline for manuscript submissions: closed (30 November 2013)

Special Issue Editors

Guest Editor
Prof. Dr. Michael Y. Sherman (Website)

Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street K-323, Boston, MA 02118, USA
Fax: +1-617-638-5339
Interests: heat shock proteins; hsf1; senescence; breast cancer
Guest Editor
Dr. Stuart K. Calderwood (Website)

Department of Radiation Oncology, Division of Molecular and Cellular Biology, Beth Israel Deaconess medical School, Harvard Medical School, Boston, MA 2215, USA
Interests: heat shock protein; molecular chaperone; HSF1; apoptosis; senescence; tumor growth; invasion; metastasis; angiogenesis; immunogenicity; ras; p53

Special Issue Information

Dear Colleagues,

Population studies and laboratory data with cells and model organisms indicate that various heat shock proteins play an important role in the genesis and progression of many cancer types. These works led to development of inhibitors of heat shock proteins, some of which have been tested in clinical trials. Since recently we have started understanding the mechanistic aspects of the role of heat shock proteins in cancer, which hopefully will teach us how to rationally combine the inhibitors with other anti-cancer drugs and what types of cancer can be treated with these inhibitors. This issue of Cancers, "Heat shock proteins in cancer: chaperones of tumorigenesis" seeks articles which will shed new light on this topic.

Prof. Dr. Michael Y. Sherman
Dr. Stuart K. Calderwood
Guest Editors

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 800 CHF (Swiss Francs).

Keywords

  • chaperones
  • heat shock proteins
  • cancer initiation
  • oncogene-induced senescence
  • cancer progression
  • metastasis
  • angiogenesis

Published Papers (6 papers)

Download All Papers
View options order results:
content type | publication date

result details:
normal | extended | compact
Displaying articles 1-6
Show export options Hide export options
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Heat Shock Protein 90 (HSP90) and Her2 in Adenocarcinomas of the Esophagus
by , , , and
Cancers 2014, 6(3), 1382-1393; doi:10.3390/cancers6031382
Received: 16 January 2014 / Revised: 25 April 2014 / Accepted: 16 June 2014 / Published: 27 June 2014
Cited by 3 | PDF Full-text (1177 KB) | HTML Full-text | XML Full-text
Abstract
Her2 overexpression and amplification can be found in a significant subset of esophageal adenocarcinomas. The activity of Her2 has been shown to be modulated by molecular chaperones such as HSP90. We analyzed expression/amplification data for HSP90 and Her2 on 127 primary resected [...] Read more.
Her2 overexpression and amplification can be found in a significant subset of esophageal adenocarcinomas. The activity of Her2 has been shown to be modulated by molecular chaperones such as HSP90. We analyzed expression/amplification data for HSP90 and Her2 on 127 primary resected esophageal adenocarcinomas in order to evaluate a possible relationship between these two molecules. HSP90 expression determined by immunohistochemistry was observed in various levels. Thirty nine (39) tumors (30.7%) were classified as Her2-positive according to their immunoreactivity and amplification status. There was a significant correlation between HSP90 expression and Her2-status (p = 0.008). This could also be demonstrated by quantitative protein expression analysis with reverse phase protein arrays (r = 0.9; p < 0.001). Her2-status was associated withpT-category (p = 0.041), lymph node metastases (p = 0.049) and tumor differentiation (p = 0.036) with a higher percentage of cases with negative Her2 status in lower tumor stagesA negative Her2-status was also associated with better survival in univariate and multivariate analysis (p = 0.001 and p = 0.014). For HSP90, no associations between clinical and pathological parameters were found. The observed association between HSP90 expression and Her2 suggests a co-regulation of these molecules in at least a subset of esophageal adenocarcinomas. Anti-HSP90 drugs, which recently have been introduced in cancer treatment, may also be an option for these tumors by targeting HSP90 alone or in combination with Her2. Full article
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)
Open AccessArticle An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein
by , , , and
Cancers 2014, 6(2), 1031-1046; doi:10.3390/cancers6021031
Received: 12 December 2013 / Revised: 12 March 2014 / Accepted: 8 April 2014 / Published: 30 April 2014
Cited by 4 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text
Abstract
Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital [...] Read more.
Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion. Full article
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)
Open AccessArticle Heat Shock Response Associated with Hepatocarcinogenesis in a Murine Model of Hereditary Tyrosinemia Type I
by , , , and
Cancers 2014, 6(2), 998-1019; doi:10.3390/cancers6020998
Received: 6 December 2013 / Revised: 15 March 2014 / Accepted: 3 April 2014 / Published: 23 April 2014
Cited by 3 | PDF Full-text (1072 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Hereditary Tyrosinemia type 1 (HT1) is a metabolic liver disease caused by genetic defects of fumarylacetoacetate hydrolase (FAH), an enzyme necessary to complete the breakdown of tyrosine. The severe hepatic dysfunction caused by the lack of this enzyme is prevented by the [...] Read more.
Hereditary Tyrosinemia type 1 (HT1) is a metabolic liver disease caused by genetic defects of fumarylacetoacetate hydrolase (FAH), an enzyme necessary to complete the breakdown of tyrosine. The severe hepatic dysfunction caused by the lack of this enzyme is prevented by the therapeutic use of NTBC (2-[2-nitro-4-(trifluoromethyl)benzoyl] cyclohexane-1,3-dione). However despite the treatment, chronic hepatopathy and development of hepatocellular carcinoma (HCC) are still observed in some HT1 patients. Growing evidence show the important role of heat shock proteins (HSPs) in many cellular processes and their involvement in pathological diseases including cancer. Their survival-promoting effect by modulation of the apoptotic machinery is often correlated with poor prognosis and resistance to therapy in a number of cancers. Here, we sought to gain insight into the pathophysiological mechanisms associated with liver dysfunction and tumor development in a murine model of HT1. Differential gene expression patterns in livers of mice under HT1 stress, induced by drug retrieval, have shown deregulation of stress and cell death resistance genes. Among them, genes coding for HSPB and HSPA members, and for anti-apoptotic BCL-2 related mitochondrial proteins were associated with the hepatocarcinogenetic process. Our data highlight the variation of stress pathways related to HT1 hepatocarcinogenesis suggesting the role of HSPs in rendering tyrosinemia-affected liver susceptible to the development of HCC. Full article
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)

Review

Jump to: Research

Open AccessReview The Double-Edged Sword: Conserved Functions of Extracellular Hsp90 in Wound Healing and Cancer
by , and
Cancers 2014, 6(2), 1065-1097; doi:10.3390/cancers6021065
Received: 13 March 2014 / Revised: 16 April 2014 / Accepted: 24 April 2014 / Published: 6 May 2014
Cited by 6 | PDF Full-text (1100 KB) | HTML Full-text | XML Full-text
Abstract
Heat shock proteins (Hsps) represent a diverse group of chaperones that play a vital role in the protection of cells against numerous environmental stresses. Although our understanding of chaperone biology has deepened over the last decade, the “atypical” extracellular functions of Hsps [...] Read more.
Heat shock proteins (Hsps) represent a diverse group of chaperones that play a vital role in the protection of cells against numerous environmental stresses. Although our understanding of chaperone biology has deepened over the last decade, the “atypical” extracellular functions of Hsps have remained somewhat enigmatic and comparatively understudied. The heat shock protein 90 (Hsp90) chaperone is a prototypic model for an Hsp family member exhibiting a duality of intracellular and extracellular functions. Intracellular Hsp90 is best known as a master regulator of protein folding. Cancers are particularly adept at exploiting this function of Hsp90, providing the impetus for the robust clinical development of small molecule Hsp90 inhibitors. However, in addition to its maintenance of protein homeostasis, Hsp90 has also been identified as an extracellular protein. Although early reports ascribed immunoregulatory functions to extracellular Hsp90 (eHsp90), recent studies have illuminated expanded functions for eHsp90 in wound healing and cancer. While the intended physiological role of eHsp90 remains enigmatic, its evolutionarily conserved functions in wound healing are easily co-opted during malignancy, a pathology sharing many properties of wounded tissue. This review will highlight the emerging functions of eHsp90 and shed light on its seemingly dichotomous roles as a benevolent facilitator of wound healing and as a sinister effector of tumor progression. Full article
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)
Open AccessReview HspB1, HspB5 and HspB4 in Human Cancers: Potent Oncogenic Role of Some of Their Client Proteins
by and
Cancers 2014, 6(1), 333-365; doi:10.3390/cancers6010333
Received: 11 November 2013 / Revised: 3 January 2014 / Accepted: 17 January 2014 / Published: 7 February 2014
Cited by 15 | PDF Full-text (1086 KB) | HTML Full-text | XML Full-text
Abstract
Human small heat shock proteins are molecular chaperones that regulate fundamental cellular processes in normal unstressed cells as well as in many cancer cells where they are over-expressed. These proteins are characterized by cell physiology dependent changes in their oligomerization and phosphorylation [...] Read more.
Human small heat shock proteins are molecular chaperones that regulate fundamental cellular processes in normal unstressed cells as well as in many cancer cells where they are over-expressed. These proteins are characterized by cell physiology dependent changes in their oligomerization and phosphorylation status. These structural changes allow them to interact with many different client proteins that subsequently display modified activity and/or half-life. Nowdays, the protein interactomes of small Hsps are under intense investigations and will represent, when completed, key parameters to elaborate therapeutic strategies aimed at modulating the functions of these chaperones. Here, we have analyzed the potential pro-cancerous roles of several client proteins that have been described so far to interact with HspB1 (Hsp27) and its close members HspB5 (αB-crystallin) and HspB4 (αA-crystallin). Full article
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)
►▼ Figures

Open AccessReview The Complex Function of Hsp70 in Metastatic Cancer
by , , , , , and
Cancers 2014, 6(1), 42-66; doi:10.3390/cancers6010042
Received: 7 November 2013 / Revised: 5 December 2013 / Accepted: 11 December 2013 / Published: 20 December 2013
Cited by 17 | PDF Full-text (968 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Elevated expression of the inducible heat shock protein 70 (Hsp70) is known to correlate with poor prognosis in many cancers. Hsp70 confers survival advantage as well as resistance to chemotherapeutic agents, and promotes tumor cell invasion. At the same time, tumor-derived extracellular [...] Read more.
Elevated expression of the inducible heat shock protein 70 (Hsp70) is known to correlate with poor prognosis in many cancers. Hsp70 confers survival advantage as well as resistance to chemotherapeutic agents, and promotes tumor cell invasion. At the same time, tumor-derived extracellular Hsp70 has been recognized as a “chaperokine”, activating antitumor immunity. In this review we discuss localization dependent functions of Hsp70 in the context of invasive cancer. Understanding the molecular principles of metastasis formation steps, as well as interactions of the tumor cells with the microenvironment and the immune system is essential for fighting metastatic cancer. Although Hsp70 has been implicated in different steps of the metastatic process, the exact mechanisms of its action remain to be explored. Known and potential functions of Hsp70 in controlling or modulating of invasion and metastasis are discussed. Full article
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)
Displaying articles 1-6
Show export options Hide export options
Select all
Export citation of selected articles as:

Journal Contact

MDPI AG
Cancers Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
cancers@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Cancers

About Us

Terms and Conditions Privacy Policy Contact MDPI Jobs at MDPI

Further Information

For Authors For Reviewers For Editors For Librarians For Publishers Article Processing Charges Open Access Policy

MDPI Initiatives

Institutional Membership Sciforum Preprints Scilit MDPI Books MDPI Blog

Follow MDPI

LinkedIn Facebook Twitter Google+
Back to Top