Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage

Biochemical and Biophysical Research Communications
Yan Nan ShenKee-Ho Lee

Abstract

Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells.

References

Dec 1, 1990·International Journal of Radiation Biology·C S Potten
Oct 15, 1982·Biochemical and Biophysical Research Communications·E A Turley
May 30, 1997·The Journal of Biological Chemistry·P H WeigelM Tammi
Mar 30, 2001·The Journal of Biological Chemistry·V B LokeshwarB L Lokeshwar
Nov 22, 2001·The Journal of Biological Chemistry·Eva A TurleyLilly Y W Bourguignon
Sep 5, 2003·The Journal of Biological Chemistry·Alexandra Zoltan-JonesBryan P Toole
Jun 30, 2006·The Journal of Biological Chemistry·Amy C CookAlan B Tuck
Feb 23, 2007·International Journal of Cancer. Journal International Du Cancer·Yuejuan LiParaskevi Heldin
Nov 6, 2007·The Journal of Biological Chemistry·Paul H Weigel, Paul L DeAngelis
May 20, 2008·Seminars in Cancer Biology·Robert Stern
Mar 26, 2010·Radiation Research·Jacqueline P WilliamsWilliam H McBride
Mar 2, 2011·The American Journal of Pathology·Steven J Wang, Lilly Y W Bourguignon
Mar 3, 2011·The FEBS Journal·Raija H TammiMarkku I Tammi
Jul 15, 2011·Journal of Dermatological Science·Megumi TobiishiShintaro Inoue
Nov 1, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Terrence E RiehlWilliam F Stenson

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Citations

Aug 19, 2016·Journal of Cancer Research and Clinical Oncology·Ruo-Lin WuXiao-Ping Geng
Nov 3, 2021·Experimental Dermatology·Romana ŠínováKristina Nešporová

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