Wang Yin, Jerome Nicole A, Kelleher Alan J, Henderson Marian L, Day Mark L, Coulombe Pierre A, Palmbos Phillip L
Department of Internal Medicine, Hematology/Oncology Division, University of Michigan Medical School, Ann Arbor, MI, USA.
Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Oncogene. 2025 Sep 4. doi: 10.1038/s41388-025-03557-z.
Bladder cancer is a common malignancy whose lethality is determined by invasive potential. We have previously shown that TRIM29, also known as ATDC, is transcriptionally regulated by TP63 in basal bladder cancers where it promotes invasive progression and metastasis, but the molecular events which promote invasion and metastasis downstream of TRIM29 remained poorly understood. Here we identify stimulation of bladder cancer migration as the specific role of TRIM29 during invasion. We show that TRIM29 physically interacts with K14+ intermediate filaments which, in turn, regulates focal adhesion stability. Further, we find that both K14 and the focal adhesion protein, ZYX are required for bladder cancer migration and invasion. Taken together, these results establish a role for TRIM29 in the regulation of cytoskeleton and focal adhesions during invasion and identify a pathway with therapeutic potential.
膀胱癌是一种常见的恶性肿瘤，其致死率取决于侵袭潜力。我们之前已经表明，TRIM29（也称为ATDC）在基底膀胱癌中受TP63转录调控，它促进侵袭进展和转移，但TRIM29下游促进侵袭和转移的分子事件仍知之甚少。在这里，我们确定刺激膀胱癌迁移是TRIM29在侵袭过程中的特定作用。我们表明，TRIM29与K14 +中间丝发生物理相互作用，进而调节粘着斑稳定性。此外，我们发现K14和粘着斑蛋白ZYX都是膀胱癌迁移和侵袭所必需的。综上所述，这些结果确立了TRIM29在侵袭过程中调节细胞骨架和粘着斑的作用，并确定了一条具有治疗潜力的途径。
