FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer

Author:

Ren Ruimin1ORCID,Wang Huang2ORCID,Xu Yuan3ORCID,Wu Jinfeng1ORCID,Ma Ding1ORCID,Guan Wei14ORCID

Affiliation:

1. Department of Urology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital Third Hospital of Shanxi Medical University Taiyuan China

2. Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Third Hospital of Shanxi Medical University Taiyuan China

3. Shanxi University of Chinese Medicine Taiyuan Shanxi China

4. Department of Urology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China

Abstract

AbstractProstate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT‐PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK‐8 assay, flow cytometry, wound‐healing assay, Transwell assay, and Co‐IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

Publisher

Wiley

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