The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells

Abstract

Breast cancer (BC) is one of the major causes of cancer death in women and is closely related to hormonal dysregulation. Estrogen receptor (ER)-positive BCs are generally treated with anti hormone therapy using antiestrogens or aromatase inhibitors. However, BC cells may become resistant to endocrine therapy, a process facilitated by autophagy, which may either promote or suppress tumor expansion. The autophagy facilitator HSPB8 has been found overexpressed in some BC. Here we found that HSPB8 is highly expressed and differentially modulated by natural or synthetic selective ER modulators (SERMs), in the triple-positive hormone-sensitive BC (MCF-7) cells, but not in triple-negative MDA-MB-231 BC cells. Specific SERMs induced MCF-7 cells proliferation in a HSPB8 dependent manner whereas, did not modify MDA-MB-231 cell growth. ER expression was unaffected in HSPB8-depleted MCF-7 cells. HSPB8 over-expression did not alter the distribution of MCF-7 cells in the various phases of the cell cycle. Conversely and intriguingly, HSPB8 downregulation resulted in an increased number of cells resting in the G0/G1 phase, thus possibly reducing the ability of the cells to pass through the restriction point. In addition, HSPB8 downregulation reduced the migratory ability of MCF-7 cells. None of these modifications were observed, when another small HSP (HSPB1), also expressed in MCF-7 cells, was downregulated. In conclusion, our data suggest that HSPB8 is involved in the mechanisms that regulate cell cycle and cell migration in MCF-7 cells.

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

“…There is data that this enzyme drives epithelial-tomesenchymal transition and is responsible for cell transformation into a neoplastic-like phenotype [34]. The heat shock protein family A (Hsp70) member 5 (HSPA5), also known as 78 kDa glucose regulated protein (GRP78) and immunoglobulin heavy chain-binding protein (BiP) protein as well as the heat shock 22 kDa protein 8 (HSPB8), also known as protein kinase H11 (H11) and small stress proteinlike protein HSP22, plays an important role in tumorigenesis [35][36][37][38][39].…”

HSPB8 promotes cancer cell growth by activating the ERK‑CREB pathway and is indicative of a poor prognosis in gastric cancer patients

“…HSPB8 was also found to be associated with estrogen-related cancers. Piccolella et al found that HSPB8 modulates the proliferation and migration of breast cancer cells (24). Suzuki et al found that HSPB8 regulates TGF-α-induced ovarian cancer cell migration (25).…”

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8

“…The sHSPs participate in the proteome integrity by binding to the hydrophobic regions of misfolded and non-native proteins in stressful conditions. Besides their canonical function in proteostasis, sHSPs have been involved in an increasing number of cellular functions in stress and physiological conditions such as cellular differentiation and proliferation, translation, oxidative stress regulation, cytoskeleton stabilisation, apoptosis, and autophagy [ 1 , 3 , 19 , 33 , 39 , 59 , 86 ]. Interestingly, mutations in HSPB1 and αB-crystallin, two other members of the same sHSP family, have also been associated with inherited peripheral neuropathies [ 11 , 24 , 27 , 48 , 63 , 68 ], and distal myopathy, respectively [ 28 , 53 , 82 ].…”