title: Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage.
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.
authors: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Yan Nan
authors: YN
authors: Shen
authors: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Hyun-Jin
authors: HJ
authors: Shin
authors: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Hyun-Yoo
authors: HY
authors: Joo
authors: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Eun-Ran
authors: ER
authors: Park
authors: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Su-Hyeon
authors: SH
authors: Kim
authors: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Sang-Gu
authors: SG
authors: Hwang
authors: Laboratory of Tissue Engineering, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Sang Jun
authors: SJ
authors: Park
authors: Laboratory of Tissue Engineering, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors: Chun-Ho
authors: CH
authors: Kim
authors: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea. Electronic address: khlee@kirams.re.kr.
authors: Kee-Ho
authors: KH
authors: Lee
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004790:Enzyme Induction / Q000528:radiation effects; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D011836:Radiation Tolerance; D015854:Up-Regulation / Q000235:genetics / Q000528:radiation effects
chemical_list: C468783:H2AX protein, human; D006657:Histones; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases
keywords: Anticancer target; Cancer cells; DNA damage; HAS2; Radioresistance; Radiosensitization