Inhibition of Hec1 as a novel approach for treatment of primary liver cancer

Huang, Lynn Y.L.; Chang, Chia‐Chi; Lee, Ying-Shuan; Huang, Jow Lay; Chuang, Shuang‐En; Chang, Jia‐Ming; Kao, Kuo-Jang; Lau, Gillian M.G.; Tsai, Pei-Yi; Liu, Chia-Wei; Lin, Her-Sheng; Gish, Robert G.; Lau, Johnson Y. N.

doi:10.1007/s00280-014-2540-7

Cited by 21 publications

(21 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present report revealed that TRIP13 was highly expressed in CRC tumor tissues and various CRC cell lines. High expression of TRIP13 has also been reported in head and neck cancer, as well as in prostate cancer (20,28), indicating that TRIP13 may be overexpressed in a variety of cancers, similar to other kinetochore-localized proteins (25)(26)(27). Together with the current results, those studies suggest that TRIP13 is important in the progression of multiple cancers.…”

Section: Discussionsupporting

confidence: 77%

“…Aurora B is highly expressed in lung, prostate and thyroid cancers, and deregulated aurora B promotes tumorigenesis by inducing aneuploidy (23,24). In addition to aurora B, other kinetochore proteins such as highly expressed in cancer 1 and monopolar spindle 1 kinase have also been shown to be overexpressed in certain cancers, and small molecules that inhibit the functions of these proteins are regarded as promising candidate agents for cancer treatment (25)(26)(27). These previous studies indicate the important functions of kinetochore-localized proteins for cancer progression.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

et al. 2016

View full text Add to dashboard Cite

Abstract. Thyroid hormone receptor interactor 13 (TRIP13) is a member of the ATPases associated with various cellular activities family of proteins and is highly conserved in a wide range of species. Recent studies have demonstrated that TRIP13 is critical for the inactivation of the spindle assembly checkpoint and is associated with the progression of certain cancers. In the present study, the role of TRIP13 in colorectal cancer (CRC) was examined. Reverse transcription-quantitative polymerase chain reaction analysis revealed that TRIP13 messenger RNA was highly expressed in multiple CRC tissues. The depletion of TRIP13 in CRC cells suppressed cell proliferation, migration and invasion. To determine whether the catalytic activity of TRIP13 was critical for cancer progression, an inactive mutant of TRIP13 was expressed in CRC cells. The invasion of cancer cells that expressed the mutant TRIP13 was significantly reduced compared with that of the wild type TRIP13-expressing cancer cells. These results indicate that TRIP13 could be a potential target for CRC treatment. IntroductionThe ATPases associated with various cellular activities (AAA+) family of proteins comprises a functionally different group of enzymes that are involved in an array of cellular processes, including protein degradation, protein-complex disassembly and DNA replication (1). The AAA+ proteins are present in all kingdoms, and are characterized by the presence of conserved AAA+ domains that contain Walker A and Walker B motifs, followed by a conserved region called second region of homology (2). The majority of AAA+ proteins form hexamers to exert their biological functions. The chemical energy generated by adenosine triphosphate (ATP) hydrolysis by this family of proteins induces conformational changes in the substrate proteins to modulate their functions (3,4).A previous study reported that certain AAA+ enzymes are associated with tumor progression (5). For example, reptin [also known as RuvB-like (RUVBL) 2] and pontin (RUVBL1) have been demonstrated to be overexpressed in several tumors (5). These proteins interact with c-Myc or β-catenin, thus modulating their transcriptional activities to promote tumor progression (6). AAA+ proteins hydrolyze ATP, and thus, chemical inhibitors that disrupt the activities of cancer-associated AAA+ proteins may represent promising anti-cancer drugs.Thyroid hormone receptor interactor 13 (TRIP13, also known as 16E1BP and pachytene checkpoint 2) is a member of the AAA+ family proteins and is conserved in a wide range of species (7). It was first identified as a protein that interacts with human papilloma virus E1 proteins by a yeast two-hybrid analysis, but the physiological function of the interaction remains unknown (7). Accumulating studies have demonstrated that TRIP13 plays pivotal roles in meiotic recombination and DNA repair in plants, yeast, worms and mice (8-12). TRIP13 forms a stable hexameric ring, and ATP binding, as well as ATP hydrolysis, are critical for the function of the protein (13). Previous...

show abstract

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

et al. 2016

View full text Add to dashboard Cite

show abstract

“…KNTC2 is known to serve a critical role in chromosomal segregation during M phase (8). KNTC2 is upregulated in the tumor tissues of patients with various types of cancer, including gastric cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma (HCC), breast cancer and non-small cell lung carcinoma (9)(10)(11)(12)(13)(14). In addition, small interfering RNA (siRNA)-mediated silencing of KNTC2 has been reported to suppress cell proliferation and to induce apoptotic cell death in these tumor cells (9,12).…”

Section: Introductionmentioning

confidence: 99%

shRNA‑mediated knockdown of KNTC1 suppresses cell viability and induces apoptosis in esophageal squamous cell carcinoma

et al. 2019

View full text Add to dashboard Cite

Kinetochore-associated proteins are critical components of mitotic checkpoints, which are essential for faithful chromosomal segregation and spindle assembly during cell division. Recent advances have demonstrated that kinetochore-associated proteins are upregulated and serve significant roles in the carcinogenesis of numerous types of cancer. However, the effects of kinetochore-associated protein 1 (KNTC1) on human cancer, particularly on esophageal squamous cell carcinoma (ESCC), remain unclear. The present study revealed that KNTC1 was highly expressed in ESCC cell lines. Subsequently, lentivirus-mediated short hairpin RNAs were used to knockdown KNTC1 expression in human ESCC cell lines. Cell growth and viability were measured using multiparametric high-content screening and the MTT assay, respectively. Cell apoptosis was assessed by staining cells with Annexin V-allophycocyanin and was detected using FACScan flow cytometry. The results demonstrated that knockdown of KNTC1 effectively inhibited cell viability and increased apoptosis. In addition, a gene set enrichment analysis of online ESCC datasets indicated that KNTC1 overexpression was associated with increases in the mitotic spindle and hypoxia pathways, and decreases in the DNA repair and mismatch repair pathways. The findings of the present study suggested that KNTC1 may have an essential role in mediating cell viability and apoptosis in human ESCC cells and may serve as a novel therapeutic target for ESCC.

show abstract

“…The risk signature molecules, MMP-1, CEACAM6, HYAL1, and HEC1, applied here were discovered in our previous gene expression studies and were highly elevated (35.5, 37, 13.3, and 8 times, respectively) in cancer group of hyperplastic tissues compared with cancer-free group (23). The selected molecules were also shown to promote the progression of several types of cancers by various mechanisms (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). In addition, three of the individual markers (MMP-1, CEACAM6, and HYAL1) were shown to predict cancer with varying accuracies in pilot studies (23,26,27).…”

Section: Discussionmentioning

confidence: 90%

Breast Hyperplasias, Risk Signature, and Breast Cancer

Poola

Yue

Gillespie

et al. 2019

Cancer Prevention Research

View full text Add to dashboard Cite

We address the dilemma faced by oncologists in administering preventative measures to "at risk" patients diagnosed with atypical and nonatypical hyperplasias due to lack of any molecular means of risk stratification and identifying high-risk subjects. Our study purpose is to investigate a four marker risk signature, MMP-1, CEACAM6, HYAL1, and HEC1, using 440 hyperplastic tissues for identifying high-risk subjects who will benefit from preventative therapies. We assayed the markers by IHC and combined their expression levels to obtain a composite value from 0-10, which we called a "Cancer Risk Score." We demonstrate that the four marker-based risk scores predict subsequent cancer development with an accuracy of 91% and 86% for atypical and nonatypical subjects, respectively. We have established a correlation between risk scores and cancer rates by stratifying the samples into low risk (score 0.5); intermediate risk (score 5.4), and high risk (score >5.4) groups using Kaplan-Meier survival analysis. We have evaluated cancer rates at 5, 10, and 15 years. Our results show that the average cancer rates in the first 5 years among low-and intermediate-risk groups were 2% and 15%, respectively. Among highrisk group, the average cancer rates at 5 years were 73% and 34% for atypical and nonatypical subjects, respectively. The molecular risk stratification described here assesses a patient's tumor biology-based risk level as low, intermediate, or high and for making informed treatment decisions. The outcomes of our study in conjunction with the available prophylactic measures could prevent approximately 20%-25% of sporadic breast cancers.

show abstract

Inhibition of Hec1 as a novel approach for treatment of primary liver cancer

Abstract: Inhibition of Hec1 using small molecule approach may represent a promising novel approach for the treatment of primary liver cancers.

Cited by 21 publications

References 28 publications

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

shRNA‑mediated knockdown of KNTC1 suppresses cell viability and induces apoptosis in esophageal squamous cell carcinoma

Breast Hyperplasias, Risk Signature, and Breast Cancer

Contact Info

Product

Resources

About