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Gallbladder carcinoma (GBC) is a considerable challenge because of its high metastatic potential. The tumor microenvironment is characterized by nutrient starvation, which promotes tumor metastasis. Stathmin1, an important microtubuleregulating protein, is overexpressed and promotes metastasis in GBC. It remains unclear how the harsh tumor microenvironment regulates stathmin1 expression to affect GBC metastasis. We employed glucose deficiency to mimic nutrient starvation and found that glucose deficiency upregulated stathmin1 transcription. However, glucose deficiency also promoted p27 degradation. There was a significant negative correlation between stathmin1 and p27 protein levels under glucose deficiency. Further study revealed that, under glucose deficiency, human kinase interacting with stathmin (hKIS) induced phosphorylation at Ser10 of p27 and its translocation to the cytoplasm for degradation, which upregulated the transcription factor E2F1 to promote stathmin1 transcription. hKIS knockdown significantly inhibited p27 cytoplasmic translocation and its consequent degradation. Stathmin1 knockdown significantly inhibited GBC cell migration and invasion in vitro. Our study revealed the role of the hKIS/p27/E2F1 axis in upregulating stathmin1 transcription to promote GBC cell migration and invasion under glucose deficiency conditions • We model the nutrition starvation conditions with glucose deficiency; • We found increased levels of stathmin1 of GBC in nutrition starvation condition; • Glucose deficiency induced phosphorylation of p27Kip1 at Ser10 and consequently degradation; • Phosphorylation of p27 at Ser10 promoted GBC migration and invasion; • hKIS/p27/E2F1 axis regulated stathmin1 expression and GBC cell migration and invasion under glucose deficiency conditions. [ABSTRACT FROM AUTHOR]

B Introduction: b The 8 SP th sp edition of the AJCC staging system for gallbladder cancer (GBC) has been used in clinical practice, but we have found some deficiencies in the new edition. In our modified edition, N2 disease obtained a significant subdivision and reappraisal according to T stage, and the aberrant survival reversal of stage IIIA and stage IIIB was also corrected. [Extracted from the article]