ABSTRACT
Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor- suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.
Subject(s)
Neoplasms/metabolism , Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism , Tumor Suppressor Proteins/metabolism , Adenosine Triphosphatases/metabolism , Animals , Cell Movement , Cell Proliferation , Down-Regulation , G1 Phase Cell Cycle Checkpoints , Humans , Neoplasms/genetics , Phosphorylation , Protein Kinases/metabolism , Receptor-Like Protein Tyrosine Phosphatases, Class 3/genetics , Receptors, Eph Family/metabolism , STAT3 Transcription Factor/metabolism , Tumor Suppressor Proteins/geneticsABSTRACT
AIM: To investigate the effect of hyperthermia on hypoxia-induced epithelial-mesenchymal transition (EMT) in HepG2 hepatocellular carcinoma (HCC) cells, and its mechanism. METHODS: Cells were treated with hyperthermia at 43â °C for 0.5 h, followed by incubation under hypoxic or normoxic conditions for 72 h. Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by immunofluorescence assay or Western blot. The protein and mRNA expressions of Snail were also determined by Western blot and reverse transcription-polymerase chain reaction. Cell migratory capacity was evaluated. RESULTS: Hypoxia induced EMT in HepG2 cells, which was evidenced by morphological, molecular and functional changes, including the formation of a spindle shape and the loss of cell contact. The expression of E-cadherin was decreased but the expression of vimentin was increased; also, the migratory capability was increased by 2.2 ± 0.20-fold as compared with normoxia. However, those effects were inhibited by hyperthermia pretreatment. Furthermore, protein synthesis and mRNA expression of Snail in the cells were enhanced by hypoxia as compared with normoxia, and also significantly inhibited by hyperthermia pretreatment. CONCLUSION: Hyperthermia may inhibit hypoxia-induced EMT in HepG2 HCC cells, and the mechanism may involve inhibition of induced expression of Snail.
Subject(s)
Cell Hypoxia , Epithelial-Mesenchymal Transition , Hyperthermia, Induced , Cadherins/analysis , Cell Movement , Hep G2 Cells , Humans , Snail Family Transcription Factors , Transcription Factors/analysis , Vimentin/analysisABSTRACT
BACKGROUND/AIMS: EMT plays an essential role in tumor progression and metastasis. Hyperthermia is a potent approach for cancers with low side effects. However, the effect of hyperthermia on EMT of cancer cells is unknown. METHODOLOGY: Cells were treated with TGF-ß1 and epidermal growth factor for 96 h and then exposed to hyperthermia at 43°C for 0.5 h. Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by Western blot. The protein and mRNA expressions of Snail were detected with Western blot and RT-PCR. Cell migratory capacity was evaluated. RESULTS: TGF-ß1 induced EMT in HepG2 cells, which was evidenced by morphological, molecular and functional changes, including the formation of spindle shape and the loss of cell contact. The expression of E-cadherin was decreased but the expression of vimentin increased; also, the migratory capability was increased by 2.1±0.19-fold as compared with untreated cells. However, those effects were inhibited by the treatment of hyperthermia. Furthermore, the protein and mRNA expressions of Snail induced by TGF-ß1 were also significantly inhibited by hyperthermia treatment CONCLUSIONS: Hyperthermia can inhibit TGF-ß1-induced EMT in HepG2 cells, suggesting that hyperthermia may alter the properties of metastatic potential in cancer cells and inhibit tumor metastasis.
