Abstract
Protein interactions are crucial for maintaining homeostasis. Heat shock factor 1 (HSF1), a transcription factor that interacts with various proteins, is highly expressed in squamous cell carcinoma (SCC) of the cervix. The aim of the present study was to investigate the protein interaction profile of HSF1 in cervical SCC. Proteins interacting with HSF1 in SCC tissue and non-cancerous control (Ctrl) tissue were obtained by immunoprecipitation, separated by SDS-PAGE, identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry and analyzed using bioinformatics methods. A total of 220 and 241 proteins were identified by mass spectrometry in the tissues of Ctrl and SCC samples, respectively, among which 172 were detected exclusively in SCC (Pro-S), 151 exclusively in Ctrl (Pro-C) and 69 in both groups (Pro-B). The protein interaction profiles were different in each group; the STRING database identified three proteins that interacted with HSF1 directly, including insulin-like growth factor 1 receptor and small nuclear RNA-activating protein complex subunit 4 in Pro-C and small ubiquitin-related modifier 1 in Pro-S. Functional enrichment analysis of Gene Ontology revealed that the top terms were alternative splicing in Pro-S and polymorphism in Pro-C. In Pro-S, more categories were related to protein modification, such as phosphorylation, ubiquitination and acetylation. Therefore, HSF1 may influence the occurrence and development of cervical SCC by interacting with specific proteins.
Highlights
Cervical cancer is one of the most common malignant gynecological tumors, and squamous cell carcinoma of the cervix (SCC) is the most common histological subtype [1]
In order to investigate the effect of Heat shock factor 1 (HSF1), four SCC samples with higher HSF1 expression levels than the Ctrl samples were used in the current study (Fig. S1)
The proteins were distributed as follows: 172 proteins only occurred in SCC, 151 proteins were identified only in Ctrl, and 69 proteins were identified in the two groups and were removed from further analysis (Table I)
Summary
Cervical cancer is one of the most common malignant gynecological tumors, and squamous cell carcinoma of the cervix (SCC) is the most common histological subtype [1]. Further clarification of the molecular mechanisms underlying cervical cancer may lead to the development of improved treatment options for this disease. Upon activation by a variety of stimuli such as heat shock, infection and heavy metal toxicity, HSF1 forms trimers, translocates into the nucleus and induces various heat shock proteins (HSPs) by binding to heat shock elements (HSEs) on HSP promoters [4,5]. Accumulating evidence has suggested that HSF1 is a powerful modifier of carcinogenesis; HSF1 levels are elevated in several cancers, including breast [6], ovarian [7] and cervical cancer [8]. Activated or elevated HSF1 is often associated with resistance to chemotherapy drugs or poor prognosis [9]. The underlying mechanisms of the resistance remain to be determined
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