{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T23:21:09Z","timestamp":1770592869734,"version":"3.49.0"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Technology and Innovation Commission of Shenzhen Municipality","award":["JCYJ20220531094207017"],"award-info":[{"award-number":["JCYJ20220531094207017"]}]},{"name":"Science Technology and Innovation Commission of Shenzhen Municipality","award":["JCYJ20190809104411245"],"award-info":[{"award-number":["JCYJ20190809104411245"]}]},{"name":"Science Technology and Innovation Commission of Shenzhen Municipality","award":["JCYJ20220531094217040"],"award-info":[{"award-number":["JCYJ20220531094217040"]}]},{"name":"Scientific Research Foundation of Peking University Shenzhen Hospital","award":["KYQD2023308"],"award-info":[{"award-number":["KYQD2023308"]}]},{"name":"Shenzhen Clinical Research Center for Urology and Nephrology","award":["LCYSSQ20220823091403008"],"award-info":[{"award-number":["LCYSSQ20220823091403008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: FAM64A is highly expressed in various cancers (e.g., breast cancer, ovarian cancer), indicating that it promotes tumorigenesis and progression by facilitating epithelial\u2013mesenchymal transition. In the genitourinary system, dihydrotestosterone promotes the expression of FAM64A by binding of the androgen receptor to the FAM64A promoter, thereby enhancing the proliferation, migration, and cell cycle progression of androgen-dependent prostate cancer cell lines. However, its specific role in the initiation and progression of bladder cancer remains unclear. FAM64A overexpression has been observed in cancers such as breast and prostate; however, its role in bladder cancer (BLCA) is less understood. Muscle-invasive BLCA (MIBC) has a poor prognosis, with five-year survival rates below 50%. This study explores FAM64A\u2019s molecular mechanisms and therapeutic potential in BLCA. Methods: FAM64A expression was analyzed using TCGA data and clinical BLCA tissues. Functional assays (CCK-8, wound-healing, Transwell) assessed proliferation, migration, and invasion following FAM64A modulation. Western blotting was used to evaluate EMT markers (Vimentin, Slug) and proteins involved in the PI3K\/AKT pathway. Bioinformatics (TCGA\/GTEx) identified FAM64A-correlated genes, followed by KEGG pathway analysis. Taselisib (PI3K\/AKT inhibitor) validated pathway involvement. Results: FAM64A was upregulated in BLCA and correlated with advanced tumor stage, T-stage, and grade. Knockdown suppressed proliferation, migration, and invasion, while overexpression exacerbated these effects. FAM64A promoted G2\/M progression (via Cyclin B1\/Ki67) and EMT (via Vimentin\/Slug). KEGG analysis linked FAM64A to the PI3K\/mTORC2\/AKT signaling pathway. Taselisib reversed FAM64A-induced EMT and malignant phenotypes. Conclusions: FAM64A drives BLCA progression via PI3K\/mTORC2\/AKT-mediated EMT, serving as a potential prognostic biomarker and therapeutic target for metastatic BLCA.<\/jats:p>","DOI":"10.3390\/cancers18030540","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:32:59Z","timestamp":1770395579000},"page":"540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FAM64A Potentiates Bladder Carcinoma Tumorigenesis and Metastasis Through PI3K\/mTORC2\/AKT Pathway Activation"],"prefix":"10.3390","volume":"18","author":[{"given":"Tao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China"},{"name":"Department of Urology, PKU-Shenzhen Clinical Institute of Shantou University Medical College, Shenzhen 518036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cen","family":"Liufu","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China"},{"name":"Department of Urology, PKU-Shenzhen Clinical Institute of Shantou University Medical College, Shenzhen 518036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-4677","authenticated-orcid":false,"given":"Cong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Urology, Shenzhen Second People\u2019s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinqing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China"},{"name":"Shenzhen Clinical Research Center for Urology and Nephrology, Peking University Shenzhen Hospital, Shenzhen 518036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China"},{"name":"Shenzhen Clinical Research Center for Urology and Nephrology, Peking University Shenzhen Hospital, Shenzhen 518036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3185-1740","authenticated-orcid":false,"given":"Bentao","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology, Shenzhen Second People\u2019s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Central Laboratory, Shenzhen Qianhai Taikang Hospital, No. 3099, Menghai Avenue, Nanshan District, Shenzhen 518000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.eururo.2019.08.016","article-title":"European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)\u20142019 Update","volume":"76","author":"Babjuk","year":"2019","journal-title":"Eur. 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