SUMOylation of HSP27 regulates PKM2 to promote esophageal squamous cell carcinoma progression

Abstract

A previous proteomic screening of differentially expressed biomarkers between Kazakh patients with esophageal squamous cell carcinoma (ESCC) and normal adjacent tissues demonstrated that heat shock protein 27 (HSP27) and pyruvate kinase isoenzyme M2 (PKM2) were both highly expressed in ESCC samples compared with normal controls. However, the regulatory association between HSP27 and PKM2 in ESCC remains elusive. In the present study, immunohistochemistry and immunoblotting were adopted to examine the expression of HSP27, PKM2 and other relevant biomarkers involved in epithelial-to-mesenchymal transition in clinical tissue samples. The interactions between proteins were detected by co-immunoprecipitation (Co-IP) assay and further confirmed by immunofluorescence assay. The growth and motility of ESCC cells were examined by MTT, Transwell and wound healing assays. Overexpression of HSP27 was found to be significantly associated with T-cell classification, lymph node metastasis and poor prognosis in ESCC. In addition, HSP27 expression was significantly correlated with PKM2 expression in ESCC specimens. Functionally, knockdown of HSP27 inhibited the growth and motility of ESCC cells. Moreover, HSP27 was found to directly interact with small ubiquitin-related modified protein 2/3 (SUMO2/3) in ESCC cell lines, as evidenced by Co-IP and laser confocal imaging. In addition, downregulation of HSP27 was shown to decrease PKM2 and E-cadherin expression. Knockdown of SUMO2/3 was observed to reduce the expression of HSP27, PKM2 and EMT-related biomarkers. The results of the present study indicated that the SUMOylation of HSP27 enhances the proliferation, invasion and migration of ESCC cells via PKM2.

Plasma‑derived exosomal pyruvate kinase isoenzyme type M2 accelerates the proliferation and motility of oesophageal squamous cell carcinoma cells

“…However, whether PKM2 could be packaged and transferred in exosomes from patients with ESCC was unknown. Other studies (29,30) and our previous study (31)(32)(33) have shown that the expression of PKM2 in tumour tissues and cells was higher than that in normal-adjacent tissues and oesophageal epithelial cells, and that upregulation of the PKM2 isoform was associated with the increased Warburg effect of tumour cells (34,35). Moreover, exosomes express blastocyte-derived surface markers (36).…”

Construction of a SUMOylation regulator‐based prognostic model in low‐grade glioma

“…For example, the SUMOylation of P53 at K386 can prevent it from being acetylated by p300, but P53 acetylated by p300 can still be SUMOylated and reduce the DNA binding inhibited by SUMOylation 18 . In esophageal squamous cell carcinoma, HSP27 can directly interact with SUMO2/3, and SUMOylation of HSP27 enhances tumour cell proliferation, migration and invasion 19 . However, the research on the regulatory mechanism of SUMOylation in glioma, especially LGG is quite limited.…”

The Role of the Heat-Shock Proteins in Esophagogastric Cancer

“…In esophageal squamous cell carcinoma, HSP 27, 60, 70, and 90 seem unrelated to the risk for systemic metastasis (M stage) [ 21 , 44 , 45 ]. However, the HSP expression correlation with T and N stages is quite heterogeneous among studies.…”

“…However, the HSP expression correlation with T and N stages is quite heterogeneous among studies. Some studies show a positive relation with lymph node dissemination [ 21 , 46 ], whereas others found no significant association [ 44 ]. Some studies found a positive association with tumor depth [ 46 ], whereas others found no association [ 44 , 45 ].…”