Fig. 6: TTPAL promotes tumorigenicity and metastasis by regulating NNMT and PI3K/AKT signaling in vivo.

A MGC803 cells stably expressing TTPAL expression promoted subcutaneous tumor growth as compared to control vector, both in terms of tumor volume over the entire assay period and tumor weight at the end point. B IHC staining confirmed TTPAL overexpression in MGC803 subcutaneous xenografts, which enhanced cell proliferation (by Ki-67 staining). IHC staining results also showed that TTPAL increased NNMT and p-AKT expression in xenografts. C Western blot analysis further confirmed that TTPAL expression in MGC803 xenografts increased the expression of NNMT and phospho-AKT. D Ectopic expression of TTPAL promoted experimental metastasis of MGC803 cells in vivo. Representative images of lungs and H&E staining of lung tissues from nude mice injected with TTPAL or control vector-transfected MGC803 cells. Quantitative analysis showed that TTPAL expression significantly increased the number of metastatic lesions. E IHC staining results also showed that TTPAL enhanced cell proliferation (by Ki-67 staining) and increased NNMT and p-AKT expression in lung metastasis. F Knockdown of TTPAL significantly enhanced the inhibition of cell proliferation which mediated by 5-Fluorouracil (5 μmol/l) and paclitaxel (5 nmol/l) in AGS and MKN74 cells as indicated by MTT assay. G. Schematic illustration of the molecular mechanism of TTPAL in PI3K/AKT signaling of GC.