Wnt5a signaling is associated with aggressiveness of ER-positive breast cancer by stimulating cell migration

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10549
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: Kadoya Takayuki 広島大学, 原爆放射線医科学研究所, 講師 (20609763)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Wnt5a / 乳癌 / ALCAM / JNK

Outline of Final Research Achievements

Relationships were examined between Wnt5a expression and clinicopathologic factors in 178 consecutive cases of invasive breast cancer resected in our department between January 2011 and February 2014.Wnt5a was positively expressed in 69 cases among 178 cases of invasive breast cancer. Wnt5a expression was strongly correlated with being estrogen receptor (ER)-positive. Analysis of the relationship between Wnt5a expression and malignancy in exclusively 153 cases of ER-positive breast cancer led to detection of significant correlations with lymph node metastasis, nuclear grade, and lymphatic invasion. Relapse-free survival was shorter in cases of Wnt5a-positive breast cancer compared to Wnt5a-negative breast cancer cases (P = 0.024). MCF7 cells forced to constitutively express Wnt5a showed significantly enhanced migratory capacity as compared to control cells, whereas knockdown of Wnt5a reduced the capacity. ALCAM was identified as an Wnt5a-dependent expression molecule.

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

乳癌組織を用いた検討では、ER陽性乳癌においてWnt5aとALCAMの発現は強く相関しており、Wnt5a/ALCAM陽性乳癌はER陽性乳癌のなかで一つのグループを形成していることが考えられた。Wnt5aはER陽性乳癌における悪性化を誘導する因子であり、そのメカニズムとしてJNKを介してALCAMの発現が誘導されることが示唆された。今後は、ER陽性乳癌における悪性度、治療効果・予後予測としての因子への活用や、抗Wnt5a抗体やALCAM, Wnt5aを標的としたRNAiなど、新たな分子標的治療のターゲットとしてのさらなる検討が期待される。