| Autor: |
Yun Sun Lee, Hyung Sun Kim, HYO JUNG KIM, Hyeon Woong Kang, Da Eun Lee, Myeong Jin Kim, Woosol Chris Hong, Ju Hyun Kim, Minsoo Kim, Joon Seong Park |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2699030/v1 |
| Popis: |
Gemcitabine is considered a standard treatment for pancreatic cancer, but developing drug resistance greatly limits the effectiveness of chemotherapy and increases the rate of recurrence. Lysyl oxide-like 2 (LOXL2) is highly expressed in pancreatic cancer and is involved in carcinogenesis and EMT regulation. However, studies on the role of LOXL2 in drug resistance are limited. Here, we investigated the mechanism of LOXL2 induction and the effect of LOXL2 on EMT and CSC in gemcitabine-resistant pancreatic cancer. Glucose metabolism was activated in gemcitabine-resistant pancreatic cancer cells, and NF-κB signaling was regulated accordingly.Activated NF-κB directly induces transcription by binding to the promoters of LOXL2 and ZEB1. The EMT process was significantly inhibited by the coregulation of ZEB1 and LOXL2. In addition, LOXL2 inhibition reduced the expression of cancer stemness markers and stemness by regulating MAPK signaling activity. LOXL2 inhibits tumor growth of gemcitabine-resistant pancreatic cancer cells and increases the sensitivity to gemcitabine in mouse models. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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