ABSTRACT
BACKGROUND: Integrin αvß3 has been proposed as crucial determinant for tumor sustained progression and a molecular marker for the estimation of tumor angiogenesis. Our study suggested that integrin αvß3 could efficiently promote lung cancer cell proliferation and stem-like phenotypes in a tribbles homolog 3 (TRIB3) dependent manner. RESULT: Integrin αvß3 could mediate the activation of FAK/AKT pro-survival signaling pathway. Meanwhile, activated TRIB3 interacted with AKT to upregulated FOXO1 and SOX2 expression, resulting in sustained tumor progression in lung cancer. Our further analysis revealed that TRIB3 was significantly upregulated in lung tumor tissues and correlated with the poor outcome in clinical patients, indicating the potential role of TRIB3 in diagnostic and prognostic estimation for patients with lung cancer. CONCLUSION: Our study showed here for the first time that integrin αvß3 promote lung cancer development by activating the FAK/AKT/SOX2 axis in a TRIB3 dependent signaling pathway, and interrupting TRIB3/AKT interaction significantly improved the outcome of chemotherapy in tumor-bearing mice, representing a promising therapeutic strategy in lung cancer.
Subject(s)
Cell Cycle Proteins , Integrin alphaVbeta3 , Lung Neoplasms , Protein Serine-Threonine Kinases , Repressor Proteins , Animals , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Proliferation/genetics , Humans , Integrin alphaVbeta3/genetics , Integrin alphaVbeta3/metabolism , Lung Neoplasms/pathology , Mice , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Signal TransductionABSTRACT
The Rho kinase pathway has previously been reported to possess a close relationship with the growth, migration and invasion of lung cancer cells. However, the molecular mechanisms underlying the effects of this pathway on lung cancer cells are still elusive. The aim of the present study was to investigate the effects and underlying molecular mechanisms of Ras homolog family member A (RhoA) on the proliferation and apoptosis of SPCA1 lung carcinoma cells. Stable SPCA1 lung cancer cell lines, in which RhoA expression was silenced by small interfering RNA, were isolated following Geneticin screening. Inhibition of RhoA expression significantly decreased the proliferation of SPCA1 lung cancer cells, whereas apoptosis was significantly increased (P<0.01) as determined by the MTS tetrazolium assay and flow cytometry analysis, respectively. At the molecular level, knockdown of RhoA resulted in the significant activation of caspase3 (P<0.01), and a significant reduction in the levels of phosphorylated signal transducer and activator of transcription (phosphoSTAT3; P<0.01), as determined by western blotting. The results suggested that RhoA knockdown prevents cell proliferation and induces apoptosis in SPCA1 lung cancer cells. Furthermore, the underlying mechanisms responsible for these effects may include the activation of caspase3 and the reduction of phosphoSTAT3 levels.
Subject(s)
Apoptosis , Lung Neoplasms/metabolism , rhoA GTP-Binding Protein/metabolism , Apoptosis/genetics , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation , Gene Expression , Gene Silencing , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Phosphorylation , RNA Interference , RNA, Small Interfering , STAT3 Transcription Factor/metabolism , rhoA GTP-Binding Protein/geneticsABSTRACT
BACKGROUND: Ongoing improvements in technique and instruments for video-assisted thoracoscopic surgery (VATS) have made minimally-invasive uniportal VATS lobectomy a reality. However, the outcomes of the procedure are still under investigation, and at present, uniportal VATS lobectomy is performed infrequently at most hospitals. We have therefore reviewed our outcomes with this procedure in an attempt to validate its safety, efficacy, and feasibility. METHODS: We retrospectively analyzed and compared perioperative data for patients who underwent uniportal, two-port, and traditional three-port VATS lobectomy between January 2015 and December 2015 at our hospital. RESULTS: Among 257 patients who had successful VATS lobectomy during the study period, 73 underwent uniportal VATS, 86 underwent two-port VATS, and 98 underwent traditional three-port VATS. There were no surgical or 30-day postoperative mortalities, and no significant differences in operative times, blood loss, number of lymph nodes retrieved and nodal stations explored, drainage times, length of hospital stay, or postoperative complications among the three groups. The visual analogue scale (VAS) pain scores were significantly lower in the uniportal VATS group after surgery (P < 0.05). CONCLUSIONS: Uniportal VATS lobectomy is a safe and feasible surgical procedure that is associated with decreased surgical trauma and less postoperative pain compared to traditional VATS. Further long term follow-up analyses in large numbers of patients are ongoing.
