Abstract
Heat shock protein (Hsp)-27 is a small-sized, ATP-independent, chaperone molecule that is overexpressed under conditions of cellular stress such as oxidative stress and heat shock, and protects proteins from unfolding, thus facilitating proteostasis and cellular survival. Despite its protective role in normal cell physiology, Hsp27 overexpression in various cancer cell lines is implicated in tumor initiation, progression, and metastasis through various mechanisms, including modulation of the SWH pathway, inhibition of apoptosis, promotion of EMT, adaptation of CSCs in the tumor microenvironment and induction of angiogenesis. Investigation of the role of Hsp27 in the resistance of various cancer cell types against doxorubicin, herceptin/trastuzumab, gemcitabine, 5-FU, temozolomide, and paclitaxel suggested that Hsp27 overexpression promotes cancer cell survival against the above-mentioned chemotherapeutic agents. Conversely, Hsp27 inhibition increased the efficacy of those chemotherapy drugs, both in vitro and in vivo. Although numerous signaling pathways and molecular mechanisms were implicated in that chemotherapy resistance, Hsp27 most commonly contributed to the upregulation of Akt/mTOR signaling cascade and inactivation of p53, thus inhibiting the chemotherapy-mediated induction of apoptosis. Blockage of Hsp27 could enhance the cytotoxic effect of well-established chemotherapeutic drugs, especially in difficult-to-treat cancer types, ultimately improving patients' outcomes.