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Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond

1
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
2
Laboratory of Oncology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Mendoza 5500, Argentina
3
Department of Functional Genomics, Geisinger Medical Center, Danville, PA 17822, USA
4
Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90010, Brazil
5
Department of Surgery, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4507; https://doi.org/10.3390/ijms20184507
Received: 12 August 2019 / Revised: 6 September 2019 / Accepted: 7 September 2019 / Published: 11 September 2019
Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies. View Full-Text
Keywords: heat shock proteins; cancer; chaperome; molecular chaperones; tumor signaling; extracellular HSPs; proteotoxic stress; stress proteins in cancer; Hsp70; Hsp90 heat shock proteins; cancer; chaperome; molecular chaperones; tumor signaling; extracellular HSPs; proteotoxic stress; stress proteins in cancer; Hsp70; Hsp90
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Lang, B.J.; Guerrero-Giménez, M.E.; Prince, T.L.; Ackerman, A.; Bonorino, C.; Calderwood, S.K. Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond. Int. J. Mol. Sci. 2019, 20, 4507.

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