Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Mechanism and Impact of an Interaction Between Keratin 19 and a Regulator of Gene Expression

Award Number: R15CA213071
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/07/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2022

Group Awards By:

View Award Description

Mechanism and Impact of an Interaction Between Keratin 19 and a Regulator of Gene Expression - PROJECT SUMMARY Intermediate filament proteins make up the largest family of cytoskeletal proteins, and mutation or altered expression of intermediate filament proteins cause or significantly correlate with more than 80 human diseases. One key feature of the intermediate filament-associated diseases is altered expression profiles of genes that directly contribute to disease progression. One such disease type is epithelial cancers, where keratin intermediate filament proteins are widely used as diagnostic and prognostic markers for human patients, and select keratins promote tumor progression in animal models. In breast cancer, Keratin 19 (K19) is one of the most reliable and extensively studied diagnostic markers, and its higher expression correlates with worse patient prognosis. However, the specific impact of this biomarker in the tumor development remains unknown. Based on our preliminary data in human breast cancer cells and previous work on a related keratin in skin cancer cells, we propose that K19 regulates the expression of metastasis-related genes and promote metastatic cell behaviors through a direct interaction with hnRNP K. hnRNP K is a RNA-binding protein that regulates the expression of a host of pro-tumorigenic genes and promotes metastasis when accumulated in the cytoplasm. We hypothesize that K19 filaments function as cytoplasmic scaffolds for hnRNP K to post- transcriptionally regulate genes that promote invasive cell behaviors that lead to tumor metastasis. This proposal is aimed at uncovering the mechanistic details of how K19 and hnRNP K interact (Aim 1), and identifying the impact of K19-hnRNP K cooperation at the molecular and cellular levels, as well as the in vivo significance of their expression in tumor metastasis (Aim 2). Meeting the above aims will identify the contribution of a tumor marker towards metastasis, determine the regulatory mechanism governing expression of metastasis-associated genes, and reveal how the cytoplasmic accumulation of hnRNP K promotes metastasis. This proposal also has the potential to identify a novel regulator of intermediate filament organization. Ultimately, the knowledge gained can help develop novel therapeutic strategies to combat cancer and serve as a blueprint to better understand a myriad of diseases where intermediate filament genes are mutated or show altered expression.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$59,398 )
2023	2018	CATHOLIC UNIVERSITY OF AMERICA (THE)	620 MICHIGAN AVE NE	WASHINGTON	DC	20064	DISTRICT OF COLUMBIA	USA	Cancer Biology Research	000	1	11/17/2022	NEW	-$59,398
														Subtotal = -$59,398

Issue Date FY: 2018 ( Subtotal = $473,050 )
2018	2018	CATHOLIC UNIVERSITY OF AMERICA (THE)	620 MICHIGAN AVE NE	WASHINGTON	DC	20064	DISTRICT OF COLUMBIA	USA	Cancer Biology Research	000	1	6/7/2018	NEW	$473,050
														Subtotal = $473,050

Grand Total All Awards = $413,652

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanism and Impact of an Interaction Between Keratin 19 and a Regulator of Gene Expression

Award Number: R15CA213071

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/07/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer