scholarly journals Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression

Oncotarget ◽  
2017 ◽  
Vol 8 (7) ◽  
pp. 12290-12300 ◽  
Author(s):  
Takamichi Igarashi ◽  
Kenichiro Araki ◽  
Takehiko Yokobori ◽  
Bolag Altan ◽  
Takahiro Yamanaka ◽  
...  
2021 ◽  
Vol 151 ◽  
pp. 94-105
Author(s):  
Ying Zhu ◽  
Jianbo Tian ◽  
Xiating Peng ◽  
Xiaoyang Wang ◽  
Nan Yang ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Qing Hua ◽  
Tianjiao Li ◽  
Yixuan Liu ◽  
Xuefang Shen ◽  
Xiaoyan Zhu ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is a growing cause of cancer-related mortality worldwide. Kallikrein-related peptidase 8 (KLK8) has potential clinical values in many cancers. However, the clinicopathological significances of KLK8 in PDAC remain unknown. We explored the relationship of KLK8 to clinicopathological features of PDAC based on public databases. KLK8 expression was examined in human PDAC tissues. Cell proliferation and apoptosis were evaluated in KLK8-overexpressed human pancreatic cancer cell lines Mia-paca-2 and Panc-1. The related signaling pathways of KLK8 involved in pancreatic cancer progression were analyzed by gene set enrichment analysis (GSEA) and further verified in in vitro studies. We found that KLK8 was up-regulated in tumor tissues in the TCGA-PAAD cohort, and was an independent prognostic factor for both overall survival and disease-free survival of PDAC. KLK8 mRNA and protein expressions were increased in PDAC tissues compared with para-cancerous pancreas. KLK8 overexpression exerted pro-proliferation and anti-apoptotic functions in Mia-paca-2 and Panc-1 cells. GSEA analysis showed that KLK8 was positively associated with PI3K-Akt-mTOR and Notch pathways. KLK8-induced pro-proliferation and anti-apoptotic effects in Mia-paca-2 and Panc-1 cells were attenuated by inhibitors for PI3K, Akt, and mTOR, but not by inhibitor for Notch. Furthermore, overexpression of KLK8 in Mia-paca-2 and Panc-1 cells significantly increased epidermal growth factor (EGF) levels in the culture media. EGF receptor (EGFR) inhibitor could block KLK8-induced activation of PI3K/Akt/mTOR pathway and attenuate pro-proliferation and anti-apoptotic of KLK8 in Mia-paca-2 and Panc-1 cells. In conclusion, KLK8 overexpression exerts pro-proliferation and anti-apoptotic functions in pancreatic cancer cells via EGF signaling-dependent activation of PI3K/Akt/mTOR pathway. Upregulated KLK8 in PDAC predicts poor prognosis and may be a potential therapeutic target for PDAC.


2017 ◽  
Vol 108 (4) ◽  
pp. 795-803 ◽  
Author(s):  
Mamoru Satoh ◽  
Shigetsugu Takano ◽  
Kazuyuki Sogawa ◽  
Kenta Noda ◽  
Hideyuki Yoshitomi ◽  
...  

2010 ◽  
Vol 70 (2) ◽  
pp. 543-551 ◽  
Author(s):  
Ruo-Chia Tseng ◽  
Shih-Hua Lee ◽  
Han-Shui Hsu ◽  
Ben-Han Chen ◽  
Wan-Ching Tsai ◽  
...  

2019 ◽  
Vol 145 (5) ◽  
pp. 1147-1164 ◽  
Author(s):  
Zilong Yan ◽  
Kenoki Ohuchida ◽  
Biao Zheng ◽  
Takashi Okumura ◽  
Shin Takesue ◽  
...  

2019 ◽  
Vol 20 (9) ◽  
pp. 1290-1299
Author(s):  
Jiaqi Shi ◽  
Xin Guan ◽  
Fei Zhan ◽  
Chao Liu ◽  
Zhiwei Li ◽  
...  

2019 ◽  
Vol 121 (2) ◽  
pp. 1986-1997 ◽  
Author(s):  
Rongkun Li ◽  
Li Weng ◽  
Bingyan Liu ◽  
Lili Zhu ◽  
Xiaoxin Zhang ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (67) ◽  
pp. 111333-111345 ◽  
Author(s):  
Luguang Chen ◽  
Chao Ma ◽  
Yun Bian ◽  
Chengwei Shao ◽  
Tiegong Wang ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Qiang Yan ◽  
Chenming Ni ◽  
Yingying Lin ◽  
Xu Sun ◽  
Zhenhua Shen ◽  
...  

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.


2020 ◽  
Author(s):  
Qing Hua ◽  
Tianjiao Li ◽  
Yixuan Liu ◽  
Xuefang Shen ◽  
Xiaoyan Zhu ◽  
...  

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a growing cause of cancer-related mortality worldwide. Kallikrein-related peptidase 8 (KLK8) has potential clinical values in many cancers. However, the clinicopathological significances of KLK8 in PDAC remain unknown. Methods: The relationship of KLK8 to clinicopathological features of PDAC was investigated based on public databases. KLK8 expression was examined in human PDAC tissues. Cell proliferation and apoptosis were evaluated in KLK8-overexpressed human pancreatic cancer cell lines Mia-paca-2 and Panc-1. The related signaling pathways of KLK8 involved in pancreatic cancer progression were analyzed by gene set enrichment analysis (GSEA) and further verified in in vitro studies. Results: KLK8 was up-regulated in tumor tissues in the TCGA-PAAD cohort, and was an independent prognostic factor for both overall survival and disease-free survival of PDAC. KLK8 mRNA and protein expressions were increased in PDAC tissues compared with para-cancerous pancreas. KLK8 overexpression exerted pro-proliferation and anti-apoptotic functions in Mia-paca-2 and Panc-1 cells. GSEA analysis showed that KLK8 was positively associated with PI3K-Akt-mTOR and Notch pathways. KLK8-induced pro-proliferation and anti-apoptotic effects in Mia-paca-2 and Panc-1 cells were attenuated by inhibitors for PI3K, Akt, and mTOR, but not by inhibitor for Notch.Conclusion: KLK8 overexpression exerts pro-proliferation and anti-apoptotic functions in pancreatic cancer cells via PI3K/Akt/mTOR pathway. Upregulated KLK8 in PDAC predicts poor prognosis and may be a potential therapeutic target for PDAC.


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