km23-1 is a dynein light chain that was identified as a TGFβ receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.
The prognosis in the head and neck squamous cell carcinoma depends upon the lymphnode status, margin and distant metastasis. Tumor recurrence has been seen inspite of negative margin reported by the pathologist. This has led to the hypothesis that cells have transformed themselves genetically at the molecular level and escape the recognition of the microscopic eye and later phenotypically express as cancer during follow-up. Angiogenesis is essential for tumor growth and metastasis. Therefore, vascular endothelial growth factor (VEGF) expression increases chances for local relapse, lymph node recurrence and distant metastasis. In this study we have investigated the expression of vascular endothelial growth factor (VEGF) in tumor tissue and adjacent normal tissue and correlated their expression with lymph node metastasis. Out of 101 patients, 86 (85.1%) patients showed positive expression of VEGF in the tumour tissue. Of these 86, 67 patients showed positive expression for VEGF in the adjacent normal tissue (chi-square = 8.730, p value = 0.0003 with contingency coefficient 0.204). Of the 101 patients, 77 (76.2%) patients were found positive for the cervical lymphnodes. The Pearson correlation coefficient (r) was 0.203 with p value = 0.004 with confidence interval of r = 0.0086-0.3839. Thus increased expression of VEGF in adjacent normal tissue in the head and squamous cell carcinoma might be the cause of the tumor recurrence or a second primary disease during follow-up and can used as target for the adjuvant therapy in such patients.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers and is the third highest among cancer related deaths. Despite modest success with therapy such as gemcitabine, pancreatic cancer incidence remains virtually unchanged in the past 25 years. Among the several driver mutations for PDAC, Kras mutation contributes a central role for its development, progression and therapeutic resistance. In addition, inflammation is implicated in the development of most human cancer, including pancreatic cancer. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is recognized as a key mediator of inflammation and has been frequently observed to be upregulated in PDAC. Several lines of evidence suggest that NF-κB pathways play a crucial role in PDAC development, progression and resistance. In this review, we focused on emphasizing the recent advancements in the involvement of NF-κB in PADC’s progression and resistance. We also highlighted the interaction of NF-κB with other signaling pathways. Lastly, we also aim to discuss how NF-κB could be an excellent target for PDAC prevention or therapy. This review could provide insight into the development of novel therapeutic strategies by considering NF-κB as a target to prevent or treat PDAC.
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