Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer and the third leading cause of cancer-related deaths. Therefore, there is an urgent need for a novel molecular target for the treatment of PDAC. Kinesin family member C1 (KIFC1) belongs to the kinesin superfamily proteins and has been reported to be involved in the pathogenesis of a wide variety of carcinomas. However, the role of KIFC1 in PDAC remains unknown. This study aimed to analyze the expression and biological function of KIFC1 in PDAC. Immunohistochemically, KIFC1 was found in 37 of 81 PDAC cases (46%). A high expression of KIFC1 was significantly related to tumor size (p = 0.023) and poor overall survival (p = 0.011). Univariate and multivariate analysis indicated that KIFC1 expression was a prognostic factor in PDAC cases. As for cancer stem cell markers, KIFC1 expression tended to co-express significantly with CD44 (p < 0.01). The growth and spheroid colony formation of KIFC1 small interfering RNA (siRNA)-transfected PDAC cells were significantly lower than those of negative control siRNA-transfected cells. Therefore, our findings suggest that KIFC1 is an independent prognostic factor in PDAC and may represent a new promising therapeutic target in PDAC. 

Expression of kinesin family member C1 in pancreatic ductal adenocarcinoma affects tumor progression and stemness.

Quadruple-negative breast cancer (QNBC) lacks traditional actionable targets, including androgen receptor (AR). QNBC disproportionately afflicts and impacts patients of African genetic ancestry. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from undergoing centrosome-amplification-induced apoptosis, has been reported to be upregulated in TNBCs and African-American (AA) TNBCs. Herein, we analyzed KIFC1 RNA levels and their associations with clinical features and outcomes among AR-low and AR-high TNBC tumors in three distinct publicly available gene expression datasets and in the breast cancer gene expression database (bc-GenExMiner). KIFC1 levels were significantly higher in AR-low and basal-like TNBCs than in AR-high and non-basal-like TNBCs, irrespective of the stage, grade, tumor size, and lymph node status. KIFC1 levels were also upregulated in AR-low tumors relative to AR-high tumors among Black and premenopausal women with TNBC. High KIFC1 levels conferred significantly shorter overall survival, disease-free survival, and distant metastasis-free survival among AR-low and basal-like TNBC patients in Kaplan–Meier analyses. In conclusion, KIFC1 levels may be upregulated in AR-low tumors and, specifically, in those of African descent, wherein it may promote poor outcomes. KIFC1 may be an actionable cancer-cell-specific target for the AR-low TNBC subpopulation and could aid in alleviating racial disparities in TNBC outcomes.

Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers

Due to lack of clinical biomarkers, Triple Negative Breast Cancer (TNBC) is more likely to have spread to other tissues at time of diagnosis and therapy planning generally involves use of cytotoxic chemotherapy agents, such as Doxorubicin. We aimed to investigate possible advantages of using combination strategy using Doxorubicin alongside Abemaciclib. After determining the IC50 values for Doxorubicin (DOX) and Abemaciclib (ABE); CompuSyn and ComBenefit software were used to reveal the effect resulting from the combination of two drugs. Following the determined effect, cell death was revealed by fluorescence microscopy and a colony forming assay was performed to see the potential of even a single cancer cell with adhesive character to survive over time and form a clone of itself. Detection of changing antioxidant activity following DOX, ABE and DOX+ABE combination therapy in MDAMB231 cells was determined by measuring MDA, SOD and GSH activities. The expression of Cleaved Caspase 3, PARP, Cleaved PARP, Cdk2 and Bax, which changed as a result of DOX, ABE and DOX+ABE application, was shown by Western Blotting.Cyclin-dependent kinase inhibitors appear as promising agents in therapy planning for breast cancer due to their prominent role in cell cycle regulation, where the number of studies interrogating its efficiency in the treatment of cancer such as TNBC is limited. For this reason, in this study, we aimed to determine the impact of the combined use of the CDK4/6 inhibitors ABE and DOX on the cytotoxicity, apoptotic homeostasis, alterations in antioxidative mechanisms, and the molecular pathways that they utilize. Our results showed that when used in combination, Doxorubicin and Abemaciclib showed a synergistic effect on TNBC cell line MDA-MB-231. 

Combination therapy application of Abemaciclib with Doxorubicin in triple negative breast cancer cell line MDA-MB-231.

FOXD1 activates KIFC1 to modulate aerobic glycolysis and reinforce cisplatin resistance of breast cancer

BACKGROUND/AIM
Triple-negative breast cancer (TNBC) prevalence and risk of relapse are greatest in African American (AA) patients. Doxorubicin (DOX) and abemaciclib (ABE) synergism in Rb-positive TNBC cells (MDA-MB-231), and antagonism in Rb-negative TNBC cells (MDA-MB-468) have been previously shown. Here, we assessed Kinesin-like protein 1 (KIFC1) as an ethnic-specific prognostic biomarker of the DOX+ABE combination for the Rb-status in TNBC.


MATERIALS AND METHODS
Literature search for TNBC prognostic biomarkers in the AA population was conducted. MDA-MB-231 and MDA-MB-468 cells were exposed over 72 h to four treatment arms: 1) control (medium without drug), 2) DOX at 50% inhibitory concentration in MDA-MB-231 (0.565 μM) and MDA-MB-468 (0.121 μM), 3) ABE alone (2 μM), and 4) DOX+ABE combination at their corresponding concentrations in each cell-line. KIFC1 protein expression and temporal changes were quantified in MDA-MB-231 cells using western blot.


RESULTS
KIFC1, Kaiso, and Annexin A2 are literature-identified AA-specific TNBC prognostic biomarkers. KIFC1 was found to be uncorrelated to other proposed biomarkers, suggesting it may predict risk independently of other TNBC biomarkers. In both cell lines, DOX alone did not significantly change KIFC1 expression relative to control. Conversely, ABE reduced KIFC1 expression in MDA-MB-231 but not in MDA-MB-468 cells. The combination DOX+ABE resulted in a greatest reduction in KIFC1 in MDA-MB-231 cells with a more rapid time-to-full inhibition of KIFC1 compared to ABE alone.


CONCLUSION
Change in KIFC1 expression is primarily driven by ABE in Rb-positive TNBC cells. DOX increases ABE speed to achieve a full inhibition of KIFC1 in Rb-positive, yet, without influencing its expression in Rb-negative TNBC cells.

KIFC1: A Reliable Prognostic Biomarker in Rb-positive Triple-negative Breast Cancer Patients Treated With Doxorubicin in Combination With Abemaciclib.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Justin Varkey

Author Tools

Chat about Author

Papers

KIFC1: A Reliable Prognostic Biomarker in Rb-positive Triple-negative Breast Cancer Patients Treated With Doxorubicin in Combination With Abemaciclib.