scholarly journals Phycocyanin inhibits pancreatic cancer metastasis via suppressing epithelial‐mesenchymal transition and targeting Akt/β-catenin pathway

Neoplasma ◽  
2021 ◽  
Author(s):  
Rongrong Huang ◽  
Gaoyong Liao ◽  
Meifeng Gao ◽  
Yu Ou
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Extracellular HSP90α-LRP1 Signaling Promote Pancreatic Cancer Metastasis and Chemoresistance Via Regulating Epithelial-To-Mesenchymal Transition

2021 ◽  
Author(s):  
Nina Xue ◽  
Tingting Du ◽  
Fangfang Lai ◽  
Jing Jin ◽  
Ming Ji ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract Extracellular heat shock protein 90α (HSP90α) has been reported to promote cancer cell invasion and migration. However, whether pancreatic cancer (PC) cells expressed membrane-bound or secreted HSP90α and its underlying mechanism for PC progression were still unclear. Our study pointed out that highly invasive Capan2 cells has a higher level of secreted HSP90α, rather than membrane HSP90α, compared with those of less invasive PL45 cells. The conditioned medium of Capan2 cells or recombinant HSP90α protein was able to stimulate the migration and invasion of PL45 or capan2 cells, which could be prevented by a neutralizing anti-HSP90α antibody. Furthermore, secreted HSP90α promoted elements of epithelial-mesenchymal transition (EMT) in PL45 cells, including increases in vimentin and snail expressions, decreases in E-cadherin expression and changes in cell shape towards a mesenchymal phenotype, but these phenomena were reversed by anti-HSP90α antibody in Capan2 cells. In addition, high levels of low-density lipoprotein receptor-related protein 1 (LRP1) mRNA were associated with worsened patient survival in pancreatic adenocarcinoma. LRP1 as a receptor of eHSP90α for its stimulatory role of PC cells EMT and metastasis by activating AKT signaling. Down-regulation of LRP1 could promote chemosensitivity to gemcitabine and doxorubicin, but not to topotecan and paclitaxel in Capan2 cells. Therefore, our study reveals a critical role of secreted HSP90α on EMT events and suggests blocking secreted HSP90α underlies an aspect of metastasis and chemoresistance.

scholarly journals Orai3 Regulates Pancreatic Cancer Metastasis by Encoding a Functional Store Operated Calcium Entry Channel

2021 ◽  
Author(s):  
Samriddhi Arora ◽  
Jyoti Tanwar ◽  
Nutan Sharma ◽  
Suman Saurav ◽  
Rajender K. Motiani
Keyword(s):  
Pancreatic Cancer ◽  
Survival Time ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Mesenchymal Transition

Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate of less than 10%. Most of the PC associated deaths are due to metastasis to secondary sites. Calcium (Ca2+) signaling plays a critical role in regulating hallmarks of cancer progression including cell proliferation, migration and apoptotic resistance. Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous pathway responsible for Ca2+ influx into non-excitable cells. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in 6 PC cell lines and found that Orai3 forms a functional SOCE in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G1 phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first time reports that Orai3 drives aggressive phenotypes of PC cells i.e. migration in vitro and metastasis in vivo. Considering that Orai3 expression is inversely associated with the PC patients survival time, it appears to be a highly attractive therapeutic target.

scholarly journals CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis

2014 ◽  
Vol 13 (1) ◽  
pp. 15 ◽  
Author(s):  
Qiang Ding ◽  
Yumi Miyazaki ◽  
Koichiro Tsukasa ◽  
Shyuichiro Matsubara ◽  
Makoto Yoshimitsu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Erk Pathway ◽  
Mesenchymal Transition

scholarly journals BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial–Mesenchymal Transition

2020 ◽  
Vol 80 (6) ◽  
pp. 1279-1292 ◽  
Author(s):  
Masaki Sato ◽  
Mitsuyo Matsumoto ◽  
Yuriko Saiki ◽  
Mahabub Alam ◽  
Hironari Nishizawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1772
Author(s):  
Taek-In Oh ◽  
Mingyu Lee ◽  
Yoon-Mi Lee ◽  
Geon-Hee Kim ◽  
Daekee Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Lung Cancer ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Metastatic Lung

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial–mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of KrasG12D-driven lung cancer. Mechanistically, PGC1α predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1α and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1α-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer.

scholarly journals Downregulated F-Box/LRR-Repeat Protein 7 Facilitates Pancreatic Cancer Metastasis by Regulating Snail1 for Proteasomal Degradation

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Tang ◽  
Meng Ji ◽  
Xing Liang ◽  
Danlei Chen ◽  
Anan Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Invasion ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Proteasomal Degradation ◽  
Human Pancreatic Cancer ◽  
Mesenchymal Transition ◽  
Repeat Protein ◽  
Panc1 Cell

Pancreatic cancer (PCa) is one of the most aggressive lethal malignancies, and cancer metastasis is the major cause of PCa-associated death. F-box/LRR-repeat protein 7 (FBXL7) regulates cancer metastasis and the chemosensitivity of human pancreatic cancer. However, the clinical significance and biological role of FBXL7 in PCa have been rarely studied. In this study, we found that the expression of FBXL7 was down-regulated in PCa tissues compared with tumor-adjacent tissues, and the low expression of FBXL7 was positively associated with cancer metastasis. Functionally, overexpression of FBXL7 attenuated PANC1 cell invasion, whereas FBXL7 silencing promoted BxPC-3 cell invasion. Forced expression of FBXL7 upregulated the expression of epithelial markers (e.g., E-cadherin) and repressed the expression of mesenchymal markers (e.g., N-cadherin and Vimentin), indicating that FBXL7 negatively regulated the epithelial-mesenchymal transition (EMT) of PCa cells. Furthermore, we identified that FBXL7 repressed the expression of Snail1, a crucial transcription factor of EMT. Mechanistically, FBXL7 bound to Snail1 and promoted its ubiquitination and proteasomal degradation. In vivo studies demonstrated that FBXL7 inhibition promotes PCa metastasis. Taken together, our findings demonstrate that FBXL7 knockdown could efficiently enhance PCa metastasis by regulating Snail1-dependent EMT.

scholarly journals Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 558
Author(s):  
Jin Kyung Seok ◽  
Eun-Hee Hong ◽  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Sin-Eun Kim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Autophagic Flux ◽  
Oxidized Phospholipids ◽  
Mcf7 Cells ◽  
Mesenchymal Transition ◽  
Tumor Tissues

Oxidized phospholipids are well known to play physiological and pathological roles in regulating cellular homeostasis and disease progression. However, their role in cancer metastasis has not been entirely understood. In this study, effects of oxidized phosphatidylcholines such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) on epithelial-mesenchymal transition (EMT) and autophagy were determined in cancer cells by immunoblotting and confocal analysis. Metastasis was analyzed by a scratch wound assay and a transwell migration/invasion assay. The concentrations of POVPC and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine (PGPC) in tumor tissues obtained from patients were measured by LC-MS/MS analysis. POVPC induced EMT, resulting in increase of migration and invasion of human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF7). POVPC induced autophagic flux through AMPK-mTOR pathway. Pharmacological inhibition or siRNA knockdown of autophagy decreased migration and invasion of POVPC-treated HepG2 and MCF7 cells. POVPC and PGPC levels were greatly increased at stage II of patient-derived intrahepatic cholangiocarcinoma tissues. PGPC levels were higher in malignant breast tumor tissues than in adjacent nontumor tissues. The results show that oxidized phosphatidylcholines increase metastatic potential of cancer cells by promoting EMT, mediated through autophagy. These suggest the positive regulatory role of oxidized phospholipids accumulated in tumor microenvironment in the regulation of tumorigenesis and metastasis.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

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