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Review
. 2020 Jan;44(1):2-13.
doi: 10.1002/cbin.11209. Epub 2019 Aug 11.

EGFR signaling pathway occupies an important position in cancer-related downstream signaling pathways of Pyk2

Ting Shen  1   2 , Qiang Guo  1   2
Affiliations
Review

EGFR signaling pathway occupies an important position in cancer-related downstream signaling pathways of Pyk2

Ting Shen et al. Cell Biol Int. 2020 Jan.

Abstract

Proline-rich tyrosine kinase 2 (Pyk2) is a member of focal adhesion kinase (FAK) non-receptor tyrosine kinase family and has been found to promote cancer cell survival, proliferation, migration, invasion, and metastasis. Pyk2 takes part in different carcinogenic signaling pathways to promote cancer progression, including epidermal growth factor receptor (EGFR) signaling pathway. EGFR signaling pathway is a traditional carcinogenic signaling pathway, which plays a critical role in tumorigenesis and tumor progression. FAK inhibitors have been reported to fail to get the ideal anti-cancer outcomes because of activation of EGFR signaling pathway. Better understanding of Pyk2 downstream targets and interconnectivity between Pyk2 and carcinogenic EGFR signaling pathway will help finding more effective targets for clinical anti-cancer combination therapies. Thus, the interconnectivity between Pyk2 and EGFR signaling pathway, which regulates tumor development and metastasis, needs to be elucidated. In this review, we summarized the downstream targets of Pyk2 in cancers, focused on the connection between Pyk2 and EGFR signaling pathway in different cancer types, and provided a new overview of the roles of Pyk2 in EGFR signaling pathway and cancer development.

Keywords: cancer; cell migration; intercellular communication; signal peptide/recognition particle.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

References

    1. Allen JG, Lee MR, Han CY, Scherrer J, Flynn S, Boucher C, Zhao H, O'Connor AB, Roveto P, Bauer D, Graceffa R, Richards WG, Babij P (2009) Identification of small molecule inhibitors of proline‐rich tyrosine kinase 2 (Pyk2) with osteogenic activity in osteoblast cells. Bioorg Med Chem Lett 19(17): 4924–8, 10.1016/j.bmcl.2009.07.084 - DOI - PubMed
    1. Arold ST (2011) How focal adhesion kinase achieves regulation by linking ligand binding, localization and action. Curr Opin Struct Biol 21(6): 808–3, 10.1016/j.sbi.2011.09.008 - DOI - PMC - PubMed
    1. Bagi CM, Christensen J, Cohen DP, Roberts WG, Wilkie D, Swanson T, Tuthill T, Andresen CJ (2009) Sunitinib and PF‐562,271 (FAK/Pyk2 inhibitor) effectively block growth and recovery of human hepatocellular carcinoma in a rat xenograft model. Cancer Biol Ther 8(9): 856–65, 10.4161/Cbt.8.9.8246 - DOI - PubMed
    1. Bagi CM, Roberts GW, Andresen CJ (2008) Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases. Cancer 112(10): 2313–21, 10.1002/cncr.23429 - DOI - PubMed
    1. Behmoaram E, Bijian K, Jie S, Xu Y, Darnel A, Bismar TA, Alaoui‐Jamali MA (2008) Focal adhesion kinase‐related proline‐rich tyrosine kinase 2 and focal adhesion kinase are co‐overexpressed in early‐stage and invasive ErbB‐2‐positive breast cancer and cooperate for breast cancer cell tumorigenesis and invasiveness. Am J Pathol 173(5): 1540–50, 10.2353/ajpath.2008.080292 - DOI - PMC - PubMed