Abstract
Though Forkhead box P (FOXP) transcription factors comprising of FOXP1, FOXP2, FOXP3 and FOXP4 are involved in the embryonic development, immune disorders and cancer progression, the underlying function of FOXP3 targeting CD4 + CD25+ regulatory T (Treg) cells and the dual roles of FOXP proteins as an oncogene or a tumor suppressor are unclear and controversial in cancers to date. Thus, the present review highlighted research history, dual roles of FOXP proteins as a tumor suppressor or an oncogene, their molecular networks with other proteins and noncoding RNAs, cellular immunotherapy targeting FOXP3, and clinical implications in cancer progression.
Highlights
Cancer still remains a major factor of human deaths worldwide to date [1]
Forkhead box P (FOXP) family consisting of FOXP1, FOXP2, FOXP3 and FOXP4 are involved in the embryonic development, immune disorders and cancer progression
FOXP1 was overexpressed with poor prognosis in diffuse large B-cell lymphoma (DLBCL), mucosa-associated lymphoid tissue lymphoma (MALT), primary cutaneous large B-cell lymphomas and follicular lymphoma as an oncogene, while FOXP1 worked in breast, lung carcinoma and U251 glioma cells as a tumor suppressor
Summary
Cancer still remains a major factor of human deaths worldwide to date [1]. It is well documented that epigenetic and genetic alterations including transcription factors, growth factors, cytokines, chemokines and proteases are critically involved in cancer progression under specific microenvironment [2]. FOXP3 promotes the immune evasion as Treg cell marker suppressing immune response against cancer, while FOXP3 at the Xp11.23 revealed good prognosis in breast cancers as a tumor suppressor [85–88] by regulating HER-2/ErbB2 [88] or SKP2 [89, 90] oncogene.
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