Deletion or loss-of-function mutation of LKB1, frequently occurring in non-small cell lung cancers (NSCLCs), is a predominant caution of NSCLC initiation and progression. However, the upstream signaling pathways governing LKB1 activation are largely unknown. Here, we report that LKB1 undergoes Aurora kinase A (AURKA)-mediated phosphorylation, which largely compromises the LKB1/AMPK signaling axis, in turn leading to the elevation of NSCLC cell proliferation, invasion and migration. Mechanically, AURKA-mediated phosphorylation of LKB1 impairs LKB1 interaction with and phosphorylation of its downstream target AMPKα, which has critical roles in governing cancer cell energy metabolic homeostasis and tumorigenesis. Clinically, AURKA displays high levels in NSCLC patients, and correlates with poor outcome of patients with lung adenocarcinoma. Pathologically, the amplification or activation of AURKA-induced impairment of the LKB1/AMPK signaling pathway contributes to NSCLC initiation and progression, highlighting AURKA as a potential therapeutic target for combatting hyperactive AURKA-driven NSCLCs.
Background:Early serum detection is of critical importance to improve the therapy for hepatocellular carcinoma (HCC), one of the most deadly cancers. Hepatitis infection is a leading cause of HCC.Methods:In the present study, we collected total serum samples with informed consent from 80 HCC patients with HBV (+)/cirrhosis (+), 80 patients with benign diseases (50 liver cirrhosis patients and 30 HBV-infected patients) and 60 healthy controls. Analysis was by using surface-enhanced laser desorption/ionisation-time-of-flight mass spectroscopy (SELDI-TOF-MS) to find new serum markers of HCC. SELDI peaks were isolated by SDS–PAGE, identified by LC-MS/MS and validated by immunohistochemistry (IHC) in liver tissues. Migration and invasion assay were performed to test the ability of cell migration and invasion in vitro.Results:SELDI-TOF-MS revealed a band at 7777 M/Z in the serum samples from HCC patients but not from healthy controls or patients with benign diseases. The protein (7777.27 M/Z) in the proteomic signature was identified as C-C motif chemokine 15 (CCL15) by peptide mass fingerprinting. A significant increase in serum CCL15 was detected in HCC patients. Functional analysis showed that HCC cell expressed CCL15, which in turn promoted HCC cell migration and invasion.Conclusion:CCL15 may be a specific proteomic biomarker of HCC, which has an important role in tumorigenesis and tumour invasion.
Conclusion: These data represent the first systematic evaluation of the T-cell compartment in WM. The qualitative and quantitative changes in the immune system seen in CLL are not found in WM; Tcell numbers, distribution and functionality seem mostly preserved even in pretreated patients. These findings are encouraging for application of T-cell directed immunotherapy in WM, especially for relapsed/refractory WM.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.