Mitohormesis Research Center, Wonju College of Medicine, Yonsei University, Wonju, Korea.
Yonsei Institute of Sports Science and Exercise Medicine, Wonju, Korea.
Sci Rep. 2020 Jul 2;10(1):10898. doi: 10.1038/s41598-020-67794-w.
Insulin resistance is associated with increased risk for and recurrence of breast cancer. Recently, Wnt1-inducible signaling pathway protein-1 (WISP-1) was reported to impair glucose metabolism and insulin sensitivity. In various cancer tissues, Wnt signaling is upregulated and induces further oncogenic and metastatic activity. However, the effects of exercise on serum levels of WISP-1 and its upstream β-catenin have not been studied in cancer patients. We investigated the effects of exercise training on Wnt signaling and insulin sensitivity in breast cancer survivors (BCS). This single-center trial randomized 46 BCS into either 12-week exercise or control groups (1:1), and included an additional 12 age-matched healthy women. Kinanthropometric parameters, serum Wnt signaling markers, and gluco-lipid profiles were evaluated before and after the intervention. Serum β-catenin and WISP-1 concentrations were significantly higher in BCS than in healthy subjects. There was a positive correlation between β-catenin and WISP-1 levels. Exercise training in BCS significantly reduced body fat and waist circumference and enhanced aerobic and muscular fitness. Exercise decreased β-catenin and WISP-1 levels and improved gluco-lipid profiles. There was a notable correlation between changes in HOMA-IR indexes and serum WISP-1, but not with β-catenin during the exercise intervention. In conclusion, a 12-week community-based exercise intervention resulted in significant reductions in serum β-catenin and WISP-1 levels, accompanied by favorable improvements in body composition, physical fitness, and biochemical parameters in BCS. We also highlight that this is the first report concerning effects of exercise on circulating β-catenin and WISP-1 levels and correlations between WISP-1 and insulin sensitivity, which could be important for determining prognoses for BCS.
胰岛素抵抗与乳腺癌的风险增加和复发有关。最近，报道 Wnt1 诱导信号通路蛋白-1（WISP-1）可损害葡萄糖代谢和胰岛素敏感性。在各种癌症组织中，Wnt 信号被上调，并诱导进一步的致癌和转移活性。然而，运动对癌症患者血清 WISP-1 及其上游β-连环蛋白水平的影响尚未研究。我们研究了运动训练对乳腺癌幸存者（BCS）中 Wnt 信号和胰岛素敏感性的影响。这项单中心试验将 46 名 BCS 随机分为 12 周运动组或对照组（1:1），并纳入了另外 12 名年龄匹配的健康女性。在干预前后评估了人体测量参数、血清 Wnt 信号标志物和糖脂谱。BCS 中的血清β-连环蛋白和 WISP-1 浓度明显高于健康受试者。β-连环蛋白和 WISP-1 水平之间存在正相关。BCS 中的运动训练显著降低了体脂肪和腰围，并增强了有氧运动和肌肉力量。运动降低了β-连环蛋白和 WISP-1 水平，并改善了糖脂谱。在运动干预期间，HOMA-IR 指数的变化与血清 WISP-1 之间存在显著相关性，但与β-连环蛋白之间没有相关性。总之，为期 12 周的基于社区的运动干预导致血清β-连环蛋白和 WISP-1 水平显著降低，同时伴有 BCS 体成分、身体适应性和生化参数的显著改善。我们还强调，这是第一个关于运动对循环β-连环蛋白和 WISP-1 水平以及 WISP-1 与胰岛素敏感性之间相关性影响的报告，这对于确定 BCS 的预后可能很重要。
