Collectively, TMEM158 was upregulated in PC and promoted PC cell proliferation, migration, and invasion through the activation of TGFβ1 and PI3K/AKT signaling pathways, highlighting its potential as a tumor promoter and a therapeutic target for PC.
In addition, YAP modulates the PC and PSC interaction via reducing the production of connective tissue growth factor (CTGF) from PCs, inhibits paracrine-mediated PSC activation under PC-PSC co-culture conditions and in turn disrupts TGF-β1-mediated tumor-stromal interactions.
S100A4 downregulation results in significant cell growth inhibition and apoptosis in response to TGF-β1, supporting a non-canonical role of S100A4 in pancreatic cancer.
Transforming growth factor, beta (TGFB) signal is considered to be a tumor suppressive pathway based on the frequent genomic deletion of the SMAD4 gene in pancreatic cancer (PC); however; the role of the activin signal, which also belongs to the TGFB superfamily, remains largely unclear.
In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT).
To show whether single nucleotide polymorphisms (SNPs) of Epidermal growth factor (EGF)-61(*)A/G, Transforming growth factor beta 1 (TGF-B1) - 509(*)T/C and Tumor necrosis factor-alpha (TNF-A) -308(*)A/G are associated with the survival rate after pancreatic cancer surgery and with the frequency of post-operative complications.
Up-regulation of L1CAM in pancreatic duct cells is transforming growth factor beta1- and slug-dependent: role in malignant transformation of pancreatic cancer.
CTGF is induced by TGFbeta in diverse cell types, but TGFbeta receptor mediated signaling is impaired in pancreatic cancers and cell lines, usually due to DPC4/Smad4 mutations which arise during the later stages of intraepithelial neoplastic progression.
Since decreased expression of ICAM-1 has been known to contribute to cancer cell escape from immunologic recognition and cytotoxicity by effector cells, the present results indicate that unknown function of TGF-beta1 in the tumor progression and metastasis of pancreatic cancer.
These data show that the crosstalk between cancer cells and stromal elements mediated by TGF-beta1 influences cell surface- and pericellular matrix-degrading potential in vitro and may contribute to pancreatic cancer progression in vivo.
In addition, in the pancreas of TGF-beta1 transgenic mice the expression of PTEN was significantly reduced (P<0.01), as compared to wildtype littermates and incubation of PANC-1 cells with TGF-beta1 decreased PTEN mRNA levels after 24 h. Inasmuch as TGF-beta1 decreases PTEN expression in human pancreatic cancer cells and human pancreatic cancers overexpress TGF-beta1, the reduced expression of PTEN in pancreatic cancer may be mediated by TGF-beta1 overexpression.