New elucidation of the mechanisms of stress-induced EMT based on the stress granule in refractory cervical cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16766
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Fujita Health University
• Principal Investigator: Utsumi Fumi 藤田医科大学, 医学部, 講師 (10749261)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 難治性子宮頸癌 / ストレス顆粒 / UBAP2L / EMT

Outline of Final Research Achievements

It is indicated that UBAP2L modulates stress granule (SG) assembly. The in vitro experiment revealed that knockdown of UBAP2L remarkably inhibited cell proliferation.
Using cervical cancer cell lines and chemo-resistant cell lines, we evaluated the SG assembly by the anticancer agent addition and UBAP2L expression and showed the possibility that resistance to the stress by the anticancer agent occurred in the cells which acquired resistance by anticancer agent exposure. We also elucidated that the overall survival in patients with low UBAP2L expression was longer than that of those with high UBAP2L expression. With radiation exposure, malignant transformation of the cervical cancer cell was promoted by epithelial-mesenchymal transition. Using tumor tissue from operation specimens of cervical cancer patients, we developed an experimental system to evaluate chemo-resistance of the patients' tumor. This helps us to elucidate the mechanisms of tumor-acquisition of chemo-resistance.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

進行子宮頸癌に対する標準治療として同時化学放射線療法 (CCRT) が確立されている。しかしCCRTは局所腫瘍を制御する能力は優れているが、遠隔転移には効果が限定的である。またCCRTあるいは放射線治療後の照射野内の再発例は化学療法の奏効率は低く、極めて予後不良とされている。癌は、低酸素、酸化ストレス、低栄養、そして曝露される抗癌剤や放射線治療のストレス下で生存する癌細胞とストレス顆粒（SG）との関わりが注目されており、抗癌剤耐性を伴う種の癌ではSG形成が過剰に形成され、細胞死が起きにくくなることが指摘されている。このメカニズムを明らかにすることで難治性子宮頸が癌の治療成績向上の一助となる。