Abstract
BackgroundChordomas are rare, slow-growing and locally aggressive bone sarcomas. At present, chordomas are difficult to manage due to their high recurrence rate, metastasis tendency and poor prognosis. The underlying mechanisms of chordoma tumorigenesis and progression urgently need to be explored to find the effective therapeutic targets. Our previous data demonstrates that EGFR plays important roles in chordoma development and CKLF-like MARVEL transmembrane domain containing (CMTM)3 suppresses gastric cancer metastasis by inhibiting the EGFR/STAT3/EMT signaling pathway. However, the roles and mechanism of CMTM3 in chordomas remain unknown.MethodsPrimary chordoma tissues and the paired adjacent non-tumor tissues were collected to examine the expression of CMTM3 by western blot. The expression of CMTM3 in chordoma cell lines was tested by Real-time PCR and western blot. CCK-8 and colony forming unit assay were performed to delineate the roles of CMTM3 in cell proliferation. Wound healing and Transwell assays were performed to assess cell migration and invasion abilities. A xenograft model in NSG mice was used to elucidate the function of CMTM3 in vivo. Signaling pathways were analyzed by western blot and IHC. RNA-seq was performed to further explore the mechanism regulated by CMTM3 in chordoma cells.ResultsCMTM3 expression was downregulated in chordoma tissues compared with paired normal tissues. CMTM3 suppressed proliferation, migration and invasion of chordoma cells in vitro and inhibited tumor growth in vivo. CMTM3 accelerated EGFR degradation, suppressed EGFR/STAT3/EMT signaling pathway, upregulated TP53 expression and enriched the TP53 signaling pathway in chordoma cells.ConclusionsCMTM3 inhibited tumorigenesis and development of chordomas through activating the TP53 signaling pathway and suppressing the EGFR/STAT3 signaling pathway, which suppressed EMT progression. CMTM3 might be a potential therapeutic target for chordomas.
Highlights
IntroductionSlow-growing and locally aggressive bone sarcomas. At present, chordomas are difficult to manage due to their high recurrence rate, metastasis tendency and poor prognosis
Chordomas are rare, slow-growing and locally aggressive bone sarcomas
CMTM3 expression is reduced in chordoma tissues and suppresses the proliferation of chordoma cells The procedure of the entire study was illustrated in Fig. 1A, which included three parts: the CMTM3 expression study, the functional study and the mechanism study
Summary
Slow-growing and locally aggressive bone sarcomas. At present, chordomas are difficult to manage due to their high recurrence rate, metastasis tendency and poor prognosis. Our previous data demonstrates that EGFR plays important roles in chordoma development and CKLF-like MARVEL transmembrane domain containing (CMTM) suppresses gastric cancer metastasis by inhibiting the EGFR/ STAT3/EMT signaling pathway. It is necessary to study the mechanism of chordoma tumorigenesis and progression and find the effective therapeutic targets for chordoma treatment. Our previous study shows that phosphorylated EGFR plays important roles in chordomas progress [10]. EGFR phosphorylation triggers downstream signaling pathways such as signal transducer and activator of transcription 3 (STAT3) [11], AKT [12] and ERK1/2 [13] pathways The activation of these signaling pathways further drives epithelial–mesenchymal transition (EMT) [14], which is a critical process in cancer metastasis [15, 16]. It is necessary and crucial to clarify how the EGFR and TP53 signaling pathway make contributions to chordoma tumorigenesis and progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
