scholarly journals Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Frédéric Couture ◽  
Kévin Ly ◽  
Christine Levesque ◽  
Anna Kwiatkowska ◽  
Samia Ait-Mohand ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Specific Inhibitor ◽  
Peptide Inhibitors ◽  
Tumor Xenograft ◽  
Prostate Cancer Progression ◽  
Wild Type ◽  
Knockdown Cell ◽  
Antiproliferative Effects ◽  
Expression Status

The overexpression as well as the critical implication of the proprotein convertase PACE4 in prostate cancer progression has been previously reported and supported the development of peptide inhibitors. The multi-Leu peptide, a PACE4-specific inhibitor, was further generated and its capability to be uptaken by tumor xenograft was demonstrated with regard to its PACE4 expression status. To investigate whether the uptake of this inhibitor was directly dependent of PACE4 levels, uptake and efflux from cancer cells were evaluated and correlations were established with PACE4 contents on both wild type and PACE4-knockdown cell lines. PACE4-knockdown associated growth deficiencies were established on the knockdown HepG2, Huh7, and HT1080 cells as well as the antiproliferative effects of the multi-Leu peptide supporting the growth capabilities of PACE4 in cancer cells.

TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

2019 ◽  
Author(s):  
Eliza E. Bitter ◽  
Michelle H. Townsend ◽  
Kary Y.F. Tsai ◽  
Carolyn I. Allen ◽  
Rachel I. Erickson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Wild Type ◽  
Cellular Invasion ◽  
Cancer Pathogenesis

Abstract 1. Background: The salvage pathway enzyme thymidine kinase 1 (TK1) is elevated in the serum of several different cancer types and higher expression is associated with more aggressive tumor grade. As a result, it has potential as a biomarker for diagnosis and prognosis. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement has not been identified. We propose to evaluate the effects of TK1 on cancer progression in vitro through measuring cellular invasion and survival of breast cancer cells.2.Methods: Breast cancer cells MDA-MB-231, HCC 1806, and MCF7 were cultured according to standard techniques. We employed the use of TK1 target siRNA and a CRISPR-Cas9 TK1 knockout plasmid to compare transfected cell lines to wild type cell lines. Protein factors in survival and invasive pathways were also tested for correlations to TK1 in BRCA RNA-seq patient data (n=1095) using the TIMER program. Cellular invasion was quantified in cell index (factor of impedance) over a 24-hour period. Cell survival was measured by apoptosis under metabolic and DNA stress using flow cytometry. All results were statistically assessed using an ANOVA or t-test in GraphPad PRISM®.3.Results: Cellular invasion assays assessing wild type and TK1 knockdown/knockout (TK1-/-) cell types showed TK1-/- cell lines had increased invasion potential (p= 0.0001). Bioinformatically, we saw a strong overall negative correlation between apoptotic factors and TK1 (p ≤ 0.05). When testing TK1 effects on cell survival we saw a protective affect under DNA stress (p ≤ 0.05), but not under metabolic stress (p= 0.0001).4.Conclusion From cell cycle analysis, we observed a shift towards S phase in TK1-/- cells. This shift to S phase would promote growth and account for the increased cellular invasion and decrease in metabolic induced stress in TK1-/- cells. We propose that cancer cells still may elicit a cancer progressive phenotype based on effects of TK1, but that a system which isolates TK1 is not effective to understand the effects. Instead, identifying protein networks inclusive of TK1 will help to elucidate its effects on cancer progression.

scholarly journals Prostate Cancer Progression: Aspirin Causes Cell Cycle Quiescence in Prostate Cancer Cells

2018 ◽  
Vol 55 ◽  
pp. S11-S12 ◽  
Author(s):  
P. Oluseyi Olalekan Olaniyi ◽  
H. Whiteland ◽  
U.K. Shah ◽  
O. Bodger ◽  
J. Verma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Cells

Cryptotanshinone-Induced p53-Dependent Sensitization of Colon Cancer Cells to Apoptotic Drive by Regulation of Calpain and Calcium Homeostasis

2020 ◽  
Vol 48 (05) ◽  
pp. 1179-1202
Author(s):  
Yue Wang ◽  
Zhu Zhang ◽  
Kathy Ka-Wai Auyeung ◽  
Chi-Hin Cho ◽  
Ken Kin-Lam Yung ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Calcium Homeostasis ◽  
Tumor Xenograft ◽  
Calpain Inhibitor ◽  
Colon Cancer Cells ◽  
Calpain Activity ◽  
Chemotherapeutic Regimen

Over-expression of calpains in tumor tissues can be associated with cancer progression. Thus, inhibition of calpain activity using specific inhibitors has become a novel approach to control tumor growth. In this study, the anticancer potential of cryptotanshinone in combination with calpain inhibitor had been investigated in colon cancer cells and tumor xenograft. Cryptotanshinone elicited an initial endoplasmic reticular (ER) stress response, whereas prolonged stress would result in the promotion of apoptosis. It was then discovered that cryptotanshinone could cause rapid and sustained increase in cytosolic calcium in colon cancer cells accompanied by early GRP78 overexpression, which could be attenuated by pre-treatment of the calcium chelator BAPTA-AM. Cryptotanshinone also facilitated an early increase in calpain activity, which could be blocked by BAPTA-AM or the calpain inhibitor PD150606. A dynamic interaction between GRP78 and calpain during the action of cryptotanshinone was unveiled. This together with the altered NF-[Formula: see text]B signaling could be abolished by calpain inhibitor. GRP78 knockdown increased the sensitivity of cancer cells to cryptotanshinone-evoked apoptosis and reduction of cancer cell colony formation. Such sensitization of drug action had been confirmed to be p53-dependent by using p53-mutated (HT-29) and p53-deficient (HCT116 p53−∕−) cells. The synergistic antitumor effect of cryptotanshinone and calpain inhibitor was further exhibited in vivo. Taken together, findings in this study exemplify a new chemotherapeutic regimen comprising cryptotanshinone and calpain inhibitor by regulation of calpain and calcium homeostasis. This has provided us with new insights in the search of a potential target-specific neoadjuvant therapy against colon cancer.

scholarly journals Cellular prostatic acid phosphatase: a protein tyrosine phosphatase involved in androgen-independent proliferation of prostate cancer

2005 ◽  
Vol 12 (4) ◽  
pp. 805-822 ◽  
Author(s):  
Suresh Veeramani ◽  
Ta-Chun Yuan ◽  
Siu-Ju Chen ◽  
Fen-Fen Lin ◽  
Juliette E Petersen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Prostatic Acid Phosphatase ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Cells ◽  
Her 2 ◽  
Androgen Independent

Human prostatic acid phosphatase (PAcP) was used as a valuable surrogate marker for monitoring prostate cancer prior to the availability of prostate-specific antigen (PSA). Even though the level of PAcP is increased in the circulation of prostate cancer patients, its intracellular level and activity are greatly diminished in prostate cancer cells. Recent advances in understanding the function of the cellular form of PAcP (cPAcP) have shed some light on its role in prostate carcinogenesis, which may have potential applications for prostate cancer therapy. It is now evident that cPAcP functions as a neutral protein tyrosine phosphatase (PTP) in prostate cancer cells and dephosphorylates HER-2/ErbB-2/Neu (HER-2: human epidermal growth factor receptor-2) at the phosphotyrosine (p-Tyr) residues. Dephosphorylation of HER-2 at its p-Tyr residues results in the down-regulation of its specific activity, which leads to decreases in growth and tumorigenicity of those cancer cells. Conversely, decreased cPAcP expression correlates with hyperphosphorylation of HER-2 at tyrosine residues and activation of downstream extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling, which results in prostate cancer progression as well as androgen-independent growth of prostate cancer cells. These in vitro results on the effect of cPAcP on androgen-independent growth of prostate cancer cells corroborate the clinical findings that cPAcP level is greatly decreased in advanced prostate cancer and provide insights into one of the molecular mechanisms involved in prostate cancer progression. Results from experiments using xenograft animal models further indicate a novel role of cPAcP as a tumor suppressor. Future studies are warranted to clarify the use of cPAcP as a therapeutic agent in human prostate cancer patients.

scholarly journals Cancer-associated cells release citrate to support tumour metastatic progression

2021 ◽  
Vol 4 (6) ◽  
pp. e202000903
Author(s):  
Konstantin Drexler ◽  
Katharina M Schmidt ◽  
Katrin Jordan ◽  
Marianne Federlin ◽  
Vladimir M Milenkovic ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Lipid Synthesis ◽  
Specific Inhibitor ◽  
Human Pancreatic Cancer ◽  
Metastatic Progression ◽  
Atp Production ◽  
Pancreatic Cancer Cells

Citrate is important for lipid synthesis and epigenetic regulation in addition to ATP production. We have previously reported that cancer cells import extracellular citrate via the pmCiC transporter to support their metabolism. Here, we show for the first time that citrate is supplied to cancer by cancer-associated stroma (CAS) and also that citrate synthesis and release is one of the latter’s major metabolic tasks. Citrate release from CAS is controlled by cancer cells through cross-cellular communication. The availability of citrate from CAS regulated the cytokine profile, metabolism and features of cellular invasion. Moreover, citrate released by CAS is involved in inducing cancer progression especially enhancing invasiveness and organ colonisation. In line with the in vitro observations, we show that depriving cancer cells of citrate using gluconate, a specific inhibitor of pmCiC, significantly reduced the growth and metastatic spread of human pancreatic cancer cells in vivo and muted stromal activation and angiogenesis. We conclude that citrate is supplied to tumour cells by CAS and citrate uptake plays a significant role in cancer metastatic progression.

scholarly journals REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells

Oncogene ◽  
2003 ◽  
Vol 22 (19) ◽  
pp. 2920-2925 ◽  
Author(s):  
Josien K Oosterhoff ◽  
Fred Penninkhof ◽  
Albert O Brinkmann ◽  
J Anton Grootegoed ◽  
Leen J Blok
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Cells ◽  
Growth Factor Signalling

scholarly journals Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yang Li ◽  
Hai Li ◽  
Xin Wei
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Cancer Progression ◽  
Aberrant Expression

Abstract Background Prostate cancer is one of the leading causes of cancer death in males. Recent studies have reported aberrant expression of lncRNAs in prostate cancer. This study explores the role of LINC00261 in prostate cancer progression. Methods The differentially expressed genes, transcription factors, and lncRNAs related to prostate cancer were predicted by bioinformatics analysis. Prostate cancer tissue samples and cell lines were collected for the determination of the expression of LINC00261 by reverse transcription quantitative polymerase chain reaction. The binding capacity of LINC00261 to the transcription factor GATA6 was detected by RIP, and GATA6 binding to the DKK3 promoter region was assessed by ChIP. In addition, luciferase reporter system was used to verify whether LINC00261 was present at the DKK3 promoter. After gain- and loss-of function approaches, the effect of LINC00261 on prostate cancer in vitro and in vivo was assessed by the determination of cell proliferation, invasion and migration as well as angiogenesis. Results LINC00261, GATA6, and DKK3 were poorly expressed in prostate cancer. LINC00261 could inhibit transcriptional expression of DKK3 by recruiting GATA6. Overexpression of LINC00261 inhibited prostate cancer cells proliferation, migration, and invasion as well as angiogenesis, which could be reversed by silencing DKK3. Furthermore, LINC00261 could also suppress the tumorigenicity of cancer cells in vivo. Conclusions Our study demonstrates the inhibitory role of LINC00261 in prostate cancer progression, providing a novel biomarker for early detection of prostate cancer.

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