CircNOLC1/KRT16 promotes colorectal cancer invasion and migration via c-met nuclear translocation and reprogramming of the oxidative pentose phosphate pathway.

Invasion and metastasis are major contributors to mortality in patients with advanced colorectal cancer; however, the underlying molecular mechanisms remain incompletely elucidated. In this study, we demonstrate that the physical interaction between circular RNA NOLC1 (circNOLC1) and keratin 16 (KRT16) plays a pivotal role in promoting the invasive and migratory capacity of colorectal cancer cells. Silencing either circNOLC1 or KRT16 significantly reduced levels of key intermediate metabolites associated with the oxidative pentose phosphate pathway (oxoxPPP), thereby suppressing tumor cell invasion and migration. Moreover, the circNOLC1-KRT16 complex upregulates c-Met expression while concurrently inhibiting its nuclear translocation. This dual regulatory effect enhances glucose-6-phosphate dehydrogenase activity and potently activates the oxoxPPP during colorectal cancer progression. Collectively, these findings uncover a previously unrecognized circNOLC1-KRT16-c-Met- glucose-6-phosphate dehydrogenase axis that drives oxoxPPP-dependent invasion and migration in colorectal cancer, highlighting this signaling cascade as a promising therapeutic target for precision oncology.