Abstract
BackgroundNucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer. Karyopherin alpha 7 (KPNA7), the newest member of the karyopherin alpha nuclear importer family, is expressed at a high level during embryogenesis, reduced to very low or absent levels in most adult tissues but re-expressed in cancer cells.MethodsWe used siRNA-based knock-down of KPNA7 in cancer cell lines, followed by functional assays (proliferation and cell cycle) and immunofluorescent stainings to determine the role of KPNA7 in regulation of cancer cell growth, proper mitosis and nuclear morphology.ResultsIn the present study, we show that the silencing of KPNA7 results in a dramatic reduction in pancreatic and breast cancer cell growth, irrespective of the endogenous KPNA7 expression level. This growth inhibition is accompanied by a decrease in the fraction of S-phase cells as well as aberrant number of centrosomes and severe distortion of the mitotic spindles. In addition, KPNA7 depletion leads to reorganization of lamin A/C and B1, the main nuclear lamina proteins, and drastic alterations in nuclear morphology with lobulated and elongated nuclei.ConclusionsTaken together, our data provide new important evidence on the contribution of KPNA7 to the regulation of cancer cell growth and the maintenance of nuclear envelope environment, and thus deepens our understanding on the impact of nuclear transfer proteins in cancer pathogenesis.
Highlights
Nucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer
Karyopherin alpha 7 (KPNA7) is essential for pancreatic and breast cancer cell proliferation We previously showed that amplification and subsequent overexpression of KPNA7 leads to promotion of cell growth in Hs700T and AsPC-1 pancreatic cancer cell lines [28]
KPNA7 was silenced in these cell lines as well as the Hs700T cells with small interfering RNA (siRNA) leading to a minimum of 80% decrease in mRNA levels (Additional file 1: Table S3)
Summary
Nucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer. KPNA2 overexpression is already present in early lesions indicating that it is not merely a marker of advanced disease but actively participates in the pathogenesis process [15]. This notion is supported by functional studies where enhanced KPNA2 expression leads to increased cell proliferation and migration [15]. KPNA4 was recently shown to promote the migration and metastatic potential of prostate cancer cells [17]. These data illustrate that alterations in nuclear transport are important players in cancer pathogenesis
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 call
