The stress response paradox: fighting degeneration at the cost of cancer

Abstract

In the modern research era, sequencing and high-throughput analysis have linked genetic factors with a multitude of disease states. Often times, the same cellular machinery is implicated in several different diseases and has made it challenging to drug a particular disease with minimal pleotropic consequences. It is intriguing to see how different fields of disease research can present such differing views when describing the same biological process, pathway, or molecule. As observations in one field converge with research in another, we gain a more complete picture of a biological system and can accurately assess the feasibility for translational science. As an example discussed here, modulating latent stress response pathways within the cell provides exciting therapeutic potential, however, opposing views have emerged in the fields of degenerative disease and cancer. This at first glance seems logical as suppression of degenerative disease entails maintaining cell viability, while cancer aims to enhance selective senescence and cell death. As both of these disciplines seek novel therapeutic interventions, we should not overlook how scientific biases involving one biological process may impact different disease paradigms.

Proteotoxic Stress Desensitizes TGF-beta Signaling Through Receptor Downregulation in Retinal Pigment Epithelial Cells

“…Proteotoxic stress can trigger a complex of response pathways in the cytosol [ 46 , 47 ], endoplasmic reticulum [ 48 ], mitochondria [ 49 ], and nucleus [ 50 ] to restore or enhance proper protein folding and dampen cytotoxicity [ 51 ]. Proteotoxic stress has been extensively studied in neurodegeneration, cancer, aging, cardiovascular diseases.…”

Small Heat Shock Proteins in Cancers: Functions and Therapeutic Potential for Cancer Therapy

“…Furthermore, HspB1 exhibited an alteration of its degree of phosphorylation when treatment with vinblastine, paclitaxel, and doxorubicin in breast cancer cells and serine 59 phosphorylation of HspB1 induced apoptosis of vinblastine-treated breast cancer cells [73], suggesting that specifically inducing the phosphorylation of HspB1 can improve therapeutic outcomes by circumventing the drug resistance of breast cancer. Artificial overexpression of HspB1 increased doxorubicin resistance of breast cancer cells [15], cisplatin and doxorubicin resistance of testis tumor cells [59], and 17-AAG resistance of cervical cancer cells [123]. Similarly, knockdown of HspB1 decreased doxorubicin resistance of breast cancer cells [15] and 17-AAG resistance of cervical cancer cells [123].…”

“…[15]. However, HspB1 was also suggested as a suppressor for cell proliferation in human testis tumor cells [59]. HspB5 overexpression has been reported to promote tumor growth of xenografts derived from breast cancer cells [60].…”

“…Studies have shown that overexpression of HspB1 promotes cell proliferation and growth of breast cancer cells in vitro [ 15 ]. However, HspB1 was also suggested as a suppressor for cell proliferation in human testis tumor cells [ 59 ]. HspB5 overexpression has been reported to promote tumor growth of xenografts derived from breast cancer cells [ 60 ].…”

The FEBS Journal in 2018 – putting a bit of color in your life, and your figures

“…We have also published many outstanding ‘Viewpoint’ articles during the past year, including Viewpoints by Thiru Kanneganti and colleagues on inflammasome activation by nucleic acids and nucleosomes , Luis Moita and colleagues on the initiation of inflammation by homeostatic perturbations , Bernhard Rupp and colleagues on correcting the record of structural publications , Kvido Strisovsky on intramembrane proteolysis , Hakan Norell and colleagues on intratumor heterogeneity , and Peter Douglas and colleagues on the stress response and cancer . Viewpoints discuss controversial or personal perspectives on a topic and are typically in fast‐moving research areas.…”