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

Abstract

Small heat shock proteins (sHSPs) are ubiquitous ATP-independent chaperones that play essential roles in response to cellular stresses and protein homeostasis. Investigations of sHSPs reveal that sHSPs are ubiquitously expressed in numerous types of tumors, and their expression is closely associated with cancer progression. sHSPs have been suggested to control a diverse range of cancer functions, including tumorigenesis, cell growth, apoptosis, metastasis, and chemoresistance, as well as regulation of cancer stem cell properties. Recent advances in the field indicate that some sHSPs have been validated as a powerful target in cancer therapy. In this review, we present and highlight current understanding, recent progress, and future challenges of sHSPs in cancer development and therapy.

The involvement of small heat shock protein in chemoresistance in ovarian cancer - in vitro study

“…The group of small HSPs is widely studied regarding their function in cellular processes particularly in the context of human diseases and cancer (Carra et al, 2017[ 8 ]; Bakthisaran et al, 2015[ 3 ]; Xiong et al, 2020[ 63 ]). The HSPB5 is responsible for the stabilization of the cytoskeleton and antiapoptotic response (Budnar et al, 2021[ 6 ]).…”

Ins and Outs of Heat Shock Proteins in Colorectal Carcinoma: Its Role in Carcinogenesis and Therapeutic Perspectives

“…sHSPs are ubiquitously expressed in different organisms, playing a significant role in cellular proliferation, differentiation, and degradation. sHSPs are not only involved in protein refolding but also play a role in attenuating the aggregation of proteins under stressful conditions [ 96 ]; therefore, they have been proposed for different types of cancer progression, including CRC, and different inhibitors are being tested for their potent anticancer effects [ 61 ]. Unlike other HSPs, sHSPs do not have ATP binding pockets to perform their function in an ATP-independent manner.…”

“…Unlike other HSPs, sHSPs do not have ATP binding pockets to perform their function in an ATP-independent manner. Otherwise, they have three main domains; a structured α-crystalline domain (ACD), an amino-terminal region (NTR), and a carboxy-terminal region (CTR) [ 96 ]. In recent years, numerous anticancer drugs have been designed to specifically target different domains of sHSPs.…”

“…The third approach utilizes aptamers that can bind to HSP27 and inhibit its dimerization. The most well-known aptamers are PA11 and PA50, which bind to HSP27 oligomers and inhibit their tumorigenic effect [ 96 ]. The effect of these aptamers has only been studied in cancers other than CRC, including prostate cancer, small cell lung cancer (SCLC), and head and neck squamous cell carcinoma [ 2 , 96 ].…”

“…The final approach that was recently identified involves the antisense oligonucleotide (ASO). The ASO OGX427 has been shown to inhibit the mRNA expression of HSP27 [ 96 ]. ASO approaches have been extensively studied in patients with prostate, bladder, ovarian, breast, and non-small cell lung cancers [ 96 ].…”