Research Summary

Sphingolipids contribute to unique biological properties, though their functions in cancer pathogenesis are largely unknown. Our analysis of 149 NSCLC specimens and 16 cell lines showed that under the tumor-suppressor miR-101 control the ceramide synthase gene CERS6 was overexpressed and associated with invasion, and that in lung cancer cells CERS6 promotes metastasis through lamellipodia formation. Targeting CERS6-dependent sphingolipid-metabolic homeostasis may provide a novel therapeutic strategy for NSCLC.

In examinations of 158 lung cancer specimens, cell cycle- and checkpoint-related genes generally showed mRNA expression increases in lung cancer, whereas POLD4, which encodes the smallest subunit of pol delta complex, showed reduced mRNA in SCLC and a portion of NSCLC patients. In the reduced expression of POLD4, the pol delta complex exhibited an impaired in vitro DNA synthesis activity, delay in cell cycle progression and activation of checkpoint proteins, elevated frequency of chromosomal gap/break formation, as well as altered activity in DNA repair. We suggest that frequent occurrence of reduced expression of POLD4 plays a role in genomic instability in lung cancer.

Cancer initiating/stem cell hypothesis may push us for radical re-consideration in cancer pathology and treatments. For example, if conventional chemotherapy targets only non- cancer initiating/stem cells, survived cancer initiating/stem cells may revive and cause recurrence. We are under attempt to identify factors that promotes cancer stemness and to develop novel cancer treatment strategies.

Heavy-ion radiotherapy may be of potential in treatment of X-ray-resistant tumors, underlying mechanisms, i.e., how it is associated with this high efficacy, is largely unknown though. We have shown that it frequently induces widespread DNA damage at ‘chromosome boundaries’. The same dose X-ray irradiation is found with less effect. Thus heavy-ion radiotherapy may cause irreversible and mortal chromosomal damages more efficiently than X-ray, and comes up with the strong cell-killing effect.

Dense plasma cell infiltration is commonly observed in chronic inflammatory diseases and malignant tumors. However, antigens produced by these plasma cells remain unidentified. We have developed an immuno-histochemical strategy to determine the target antigens in tissue sections. Our method provides the pathophysiological information that underlies types of diseases.

Contact information
Phone:+81-562-93-2440
e-mail:motosuzu*fujita-hu.ac.jp(In case of e-mail, please change * to @)
Address:1-98, Dengakugakubo, Kutsukake-cho, Toyoake-city, Aichi, 470-1192, Japan