Metastatic prostate cancer is associated with high mortality rates. Identification of metastasis-related proteins may facilitate the development of novel therapies for the treatment of metastatic disease. In the present study, we aimed to identify prostate cancer metastasis-associated membrane proteins. We developed a phage-displayed 7-mer peptide library to screen the target peptides that were specifically bound to PC-3M cells with subtractive panning from normal prostate cells and PC-3 prostate cancer cells. A novel short peptide (B04) was found to have high affinity to highly metastatic PC-3M cells. ATP synthase β subunit (ATP5B) was then identified as a binding partner of B04 on the PC-3M cell surface. ATP5B was expressed on the PC-3M cell membrane and on highly malignant human prostate cancer specimens, as shown using multiple methodologies. Furthermore, ATP5B-positive gold particles were detected on the cellular and mitochondrial membranes by immunoelectromicroscopy. These results implied the possibility that ATP5B may translocate from the inner mitochondrial membrane to the outer surface of PC-3M cells. Additional analysis showed that incubation of B04 with PC-3M cells reduced the detection of ATP5B by western blotting and flow cytometry and significantly inhibited the proliferation, invasion and metastasis of PC-3M cells. In conclusion, ATP5B, as a binding partner of a metastasis-related short peptide (B04) on prostate cancer cells, is involved in promoting prostate cancer metastasis. In conclusion, ATP5B may be a promising biomarker and therapeutic target for highly metastatic malignancies.
Ectopic ATP5B, which is located in a unique type of lipid raft caveolar structure, can be upregulated by cholesterol loading. As the structural component of caveolae, Cav-1 is a molecular hub that is involved in transmembrane signaling. In a previous study, the ATP5B-specific binding peptide B04 was shown to inhibit the migration and invasion of prostate cancer cells, and the expression of ATP5B on the plasma membrane of MDA-MB-231 cells was confirmed. The present study investigated the effect of ectopic ATP5B on the migration and invasion of MDA-MB-231 cells and examined the involvement of Cav-1. Cholesterol loading increased the level of ectopic ATP5B and promoted cell migration and invasion. These effects were blocked by B04. Ectopic ATP5B was physically colocalized with Cav-1, as demonstrated by double immunofluorescence staining and coimmunoprecipitation. After Cav-1 knockdown, the migration and invasion abilities of MDA-MB-231 cells were significantly decreased, suggesting that Cav-1 influences the function of ectopic ATP5B. Furthermore, these effects were not reversed after treatment with cholesterol. We concluded that Cav-1 may participate in MDA-MB-231 cell migration and invasion induced by binding to ectopic ATP5B.
Background: Anaplastic thyroid carcinoma (ATC) is a rare malignant tumor. In addition to the main ATC type with classical histopathological features, the other morphological types of ATC include paucicellular variant, angiomatoid, lymphoepithelioma-like, and small-cell variant. However, an ATC variant with a chondrosarcomatous component has not been reported to date. Case presentation: Computed tomography imaging of a 63-year-old male with a 2-month history of a cervical mass revealed a 4.5-cm lesion with heterogeneous enhancement in the left thyroid lobe and two smooth and homogeneous nodules in the right thyroid lobe. The patient underwent total thyroidectomy and cervical lymph node resection. Histologically, the tumor boundary in the left lobe was clear, with a few mitotically active, spindle sarcoma-like tumor cells observed in some areas. Immunohistochemically, these spindle cells were positive for vimentin and negative for cytokeratin, paired box-8, epithelial membrane antigen, calcitonin, thyroglobulin, and thyroid transcription factor-1. In other areas, abundant cartilage matrix production and irregularly shaped lobules of cartilage, often separated by fibrous bands, were observed. The chondrocytes appeared mildly/moderately atypical and contained enlarged, hyperchromatic nucleoli. One of the two nodules in the right thyroid lobe had a clear boundary and comprised some bland spindle cells in a prominently collagenous stroma with clear boundaries. The other nodule in the right thyroid lobe was completely enclosed within a thin, fibrous capsule and exhibited normofollicular and microfollicular architecture. The patient received adjuvant radiotherapy after the surgery and was free of any local or regional recurrence or distant metastases at the 8-month follow-up evaluation. Conclusions: This unusual case of ATC with chondrosarcomatous differentiation is an important addition to the morphology spectrum of ATC types.
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