Abstract
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.
Highlights
Insulin resistance is associated with increased risk for and recurrence of breast cancer
Of the 23 breast cancer survivors (BCS) initially assigned to each group, 17 subjects in the BCS-Ex group completed combined exercise training with an average participation rate of 94.8% for all sessions
Our data indicate that affected-arm circumferences were significantly reduced in the BCS-Ex group, implying the alleviation of edematous changes (Supplementary Table 3)
Summary
Insulin resistance is associated with increased risk for and recurrence of breast cancer. We investigated the effects of exercise training on Wnt signaling and insulin sensitivity in breast cancer survivors (BCS). 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 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. The cytosolic β-catenin translocates into the nucleus, binds with T cell factor/lymphoid (TCF) enhancer factor, and acts as a transcriptional cofactor This complex induces a variety of downstream target genes, including Wnt-induced secreted protein 1 (WISP-1)[10,11,12]. Therapeutic strategies targeting recovery of circulating Wnt-related protein levels are worthwhile to explore for the management of metabolic risk factors in cancer patients
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