A crosstalk between membrane trafficking and cytoskeletons in invadopodia in cancer cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06138
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Inoue Hiroki 東京薬科大学, 生命科学部, 講師 (10294448)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 浸潤突起 / 微小管 / アクチン / 小胞輸送 / 細胞外基質

Outline of Final Research Achievements

Invadopodia in invasive cancer cells are actin-enriched structures with an ability to degrade extracellular matrix (ECM) and play crucial roles in invasion and metastasis. A formation of functional invadopodia may require a crosstalk between microtubules and actin filaments, but the molecular mechanisms are not fully understood. In addition, regulatory mechanisms of the polarized transport of metalloproteinases degrading ECM at invadopodia remain elusive. In this study, we have focused on the microtubule-associated protein (MAP) that is associated with the crosstalk between microtubules and actin filaments and the SNARE proteins that function in the transport of metalloproteinases to invadopodia and revealed a part of the molecular mechanisms of invadopodia formation followed by cancer metastasis.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

がんによる死因の90％は、がん細胞の浸潤・転移が関係している。乳がんにおいても、転移の無い場合の5年生存率は99%だが、転移すると27%に低下する。本研究は、悪性度の高い乳がん細胞の浸潤転移に関わる機構の一端を分子レベルで解明したものであり、学術的な意義にとどまらず、新規の診断・治療標的として利用できる可能性も秘めている。