S100A14 promotes progression and gemcitabine resistance in pancreatic cancer.

S100 calcium binding protein A14 (S100A14) plays an important role in the progression of several types of cancer. However, its roles in pancreatic ductal adenocarcinoma (PDAC) are largely unexplored. Here, we characterized the functional roles of S100A14 in the progression and chemoresistance of PDAC. Gene expression microarray identified that S100A14 was significantly highly expressed in four pairs of human PDAC tumor compared with corresponding non-tumor tissues genes. Quantitative reverse transcription PCR (qRT-PCR), western blotting and immunohistochemical staining (IHC) showed that S100A14 was frequently overexpressed in PDAC cell lines and tissues. Moreover, expression level of S100A14 was positively correlated to advanced cancer stages. Further, Kaplan-Meier survival analysis suggested that PDAC patients with low S100A14 expression had longer overall survival in TCGA PDAC datasets. Transient overexpressing of S100A14 promoted cell proliferation, anchorage-independent colony formation, cell migration and invasion in cell lines with low endogenous S100A14 levels, while transient silencing of S100A14 inhibited cell proliferation, anchorage-independent colony formation, cell migration and invasion in cell lines with high endogenous S100A14 levels. Persistent knockdown of S100A14 by transducing shRNAs carrying lentivirus inhibited subcutaneous tumor formation in nude mice, and sensitized the PDAC cells to gemcitabine treatment. Taken together, S100A14 exhibited oncogenic properties by promoting cell proliferation, transformation, migration and invasion, and enhanced in vivo tumor growth. More importantly, inhibition of S100A14 could effectively abrogate the cancerous properties of the PDAC cells. Our study indicated that S100A14 was a valuable target for the development of therapeutic strategy, as well as a diagnostic and prognosis biomarker for PDAC patients.

Zhu H ，Gao W ，Li X ，Yu L ，Luo D ，Liu Y ，Yu X ... -  《-》

Integrinβ1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas.

Yang D ，Shi J ，Fu H ，Wei Z ，Xu J ，Hu Z ，Zhang Y ，Yan R ，Cai Q ... -  《-》

TRIM11 suppresses ferritinophagy and gemcitabine sensitivity through UBE2N/TAX1BP1 signaling in pancreatic ductal adenocarcinoma.

Gemcitabine is first-line chemotherapy for pancreatic cancer, however, the development of resistance limits its effectiveness. The tripartite motif-containing 11 (TRIM11) protein plays crucial roles in tumor development and undergoes auto-polyubiquitination to promote interactions in selective autophagy. Therefore, Understanding whether TRIM11 is involved in ferritinophagy and gemcitabine resistance in pancreatic cancer is critical in developing pancreatic cancer therapeutics. TRIM11 expression was validated by Western blot analysis, real-time polymease chain reaction, and immunohistochemical staining. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Colony formation assays were performed to investigate pancreatic ductal adenocarcinomas (PDAC) cell viability. Mouse xenograft model of PDAC cells was established to verify the role of TRIM11 in vivo. Coimmunoprecipitation was used to identify the reciprocal regulation between TRIM11 and UBE2N. In this study, we found that TRIM11 expression were higher in PDAC cells and tissues. TRIM11 overexpression promotes PDAC cell proliferation in vitro and tumor growth in vivo. Decreased expression of TRIM11 in PDAC patients is associated with decreased UBE2N and increased TAX1BP1 expression. Coimmunoprecipitation established that TRIM11 interacts and colocalizes with UBE2N. Mechanistically, TRIM11 promoted gemcitabine resistance and suppressed ferritinophagy through UBE2N-TAX1BP1 signaling. Our findings identify TRIM11 as a key regulator of TAX1BP1 signaling with a crucial role in ferritinophagy and gemcitabine resistance in PDAC.

Shang M ，Weng L ，Xu G ，Wu S ，Liu B ，Yin X ，Mao A ，Zou X ，Wang Z ... -  《-》

Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer.

Jiang SH ，Wang Y ，Yang JY ，Li J ，Feng MX ，Wang YH ，Yang XM ，He P ，Tian GA ，Zhang XX ，Li Q ，Cao XY ，Huo YM ，Yang MW ，Fu XL ，Li J ，Liu DJ ，Dai M ，Wen SY ，Gu JR ，Hong J ，Hua R ，Zhang ZG ，Sun YW ... -  《Oncotarget》

Suppression of STAT5b in pancreatic cancer cells leads to attenuated gemcitabine chemoresistance, adhesion and invasion.

Sumiyoshi H ，Matsushita A ，Nakamura Y ，Matsuda Y ，Ishiwata T ，Naito Z ，Uchida E ... -  《-》