Acquisition mechanisms of malignant phenotypes on cancer cells under the microenvironmental stress.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26870600
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry; Tumor biology
• Research Institution: Tokai University
• Principal Investigator: ENDO Hitoshi 東海大学, 医学部, 講師 (10550551)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: がん微小環境 / 低栄養 / 酸化ストレス

Outline of Final Research Achievements

Malignant tumors are exposed to microenvironments that are characterized by low levels of nutrients because the tumors tend to outgrow the existing vasculature. Therefore, cancer cells must adapt and escape these severe microenvironments to favorable growth conditions.
In the current study, we found that LKB1/AMPK signaling pathway, a master regulator of metabolic homeostasis, is activated by glucose deprivation. Activation of LKB1/AMPK induces a transcription factor Nrf2 in the nucleus, and LKB1/AMPK-mediated Nrf2 expression is involved in the regulation of oxidative stress under glucose starved conditions. We also observed that cancer cell migration and invasion ability were enhanced due to the reduction in glucose concentration in culture medium and was completely diminished by knockdown of LKB1 or AMPK. These results suggested that the activation of LKB1/AMPK is not only contributed to adaptation to severe microenvironment but also promotes cancer progression.

Free Research Field

腫瘍生物学