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Protein Expression Levels and Gemcitabine Resistance in Non-Muscle-Invasive Bladder Cancers

By Patrick Daly - Last Updated: March 21, 2022

According to a study published in the Journal of Cancer intravesical gemcitabine (GEM) chemotherapy (IGC) is effective at lowering the risk of recurrence in non-muscle-invasive bladder cancers (NMIBC), but development of resistance to GEM can occur, leading to cancer recurrence and progression. The study’s collaborators, led by Shiyu Tong, sought to identify the molecular mechanisms of GEM resistance with a label-free quantitative proteomic technique. In the article, the authors described a “potential role of NIBAN1/FAK signaling in the regulation of GEM resistance in NMIBC, which might have potential translational value in designing experimental therapeutics to treat NMIBC.”

In the study, a total of 218 proteins with different expressions were identified in patients with paired primary and post-IGC recurrent NMIBC. Utilizing the Kyoto Encyclopedia of Genes and Genomes, the researchers uncovered multiple signaling pathways that were enriched in recurrent NMIBC, including “focal adhesion.”

After observing highly increased NIBAN1 expression in several GEM-resistant cancer cell lines and post-IGC recurrent NMIBC samples, the researchers found that “manipulation of NIBAN1 expression affected the chemosensitivity to GEM in bladder cancer cell models.” As described, NIBAN1 was seen to regulate FAK signaling activation, and highly elevated FAK (pY397) expression was also seen in post-IGC recurrent NMIBC, and positively correlated with NIBAN1 expression levels. Importantly, the study’s collaborators revealed that knockdown of FAK “markedly” reduced resistance in GEM-resistant bladder cancer cells. Likewise, knockdown of NIBAN1 “disrupted FAK signaling and sensitized GEM-resistant bladder cancer cells to GEM treatment.”

Ultimately, Tong and colleagues ultimately landed on the hypothesis that NIBAN1 may disrupt FAK signaling pathway activation and thereby promote GEM resistance in bladder cancer cells. Therefore, they concluded that “targeting NIBAN1/FAK signaling may help sensitize bladder cancer cells to GEM treatment.”

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