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As a crucial component of the tumor stroma, cancer-associated fibroblasts (CAFs) deriving from normal resident tissue fibroblasts or non-fibroblastic lineage upon receiving paracrine signals from cancer cells ( Chen et al., 2019; Han et al., 2020). In addition, CAFs not only directly interacted with cancer cells, but also indirectly participated in the crosstalk with cancer in the form of paracrine signaling ( Maeda et al., 2019; Chou et al., 2012). These cells play a crucial role in the tumor events of proliferation, metastasis, angiogenesis, therapy resistance ( Biffiet al., 2020; Kobayashi et al., 2019; Su et al., 2018; Labernadie et al., 2017). CAFs serve as synthetic machines that produce many different tumor components, which represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence ( Kalluriet al., 2016) .