Thursday, November 21, 2024 11/21/2024

Protein Kinase C Signaling Mechanisms in Cancer

Award Number: R01CA081436
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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SUPPLEMENT PROJECT SUMMARY Lung squamous cell carcinoma (LSCC) is a major sub-type of lung cancer. LSCC tumors can be further sub- classified into four distinct molecular subtypes: primitive, classical, secretory and basal based on expression profiling. The LSCC molecular subtypes share similarities in gene expression profiles with distinct lung epithelial cell populations suggesting that the LSCC molecular subtypes may originate from different lung epithelial cell populations. Genomic analysis of human LSCC pre-neoplastic lesions and tumors demonstrates that 3q26 copy number gains (CNGs) and TP53 mutations are among the most prevalent early genetic alterations in LSCC, suggesting that these genetic events play an important role in the initiation and progression of LSCC. Furthermore, interrogation of The Cancer Genome Atlas (TCGA) LSCC database reveals that 3q26 CNGs are present in all four LSCC molecular subtypes suggesting that 3q26 CNGs may play a role in the molecular signaling pathways that drive the pathogenesis of these molecular subtypes. Our studies have shown that the genes SOX2, PRKCI and ECT2 are key targets of 3q26 CNGs that functionally collaborate in maintaining the transformed phenotype of human LSCC cells. Our more recent studies have demonstrated that overexpression of SOX2, PRKCI and ECT2, in the context of Trp53 loss, is sufficient to; 1) transform mouse lung basal stem cells (LBSCs) (a cell of origin for LSCC); and 2) drive formation of LBSC tumors with LSCC-like histopathology in vivo. Based on these observations, we hypothesize that co- overexpression of SOX2, PRKCI and ECT2 and Trp53 loss can cooperate to transform other putative LSCC cells of origin to develop LSCC-like tumors that exhibit signaling pathways observed in the four human LSCC molecular subtypes. This hypothesis will be tested through two interrelated specific aims designed to; 1) assess cooperative oncogenic activities of SOX2, PRKCI and ECT2 on the transformation of putative LSCC cells of origin; and 2) determine the mechanisms underlying the roles of SOX2, PRKCI and ECT2 in lung epithelial cell transformation and LSCC development. Successful completion of these aims will provide important mechanistic insight into the molecular heterogeneity of LSCC and offer novel pre-clinical models to identify and evaluate therapeutic targets in distinct molecular subtypes of LSCC.


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: 2025 ( Subtotal = -$53,444 )
2025	2022	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	000	25	11/5/2024	NON-COMPETING CONTINUATION	-$53,444
														Subtotal = -$53,444

Issue Date FY: 2022 ( Subtotal = $469,424 )
2022	2022	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	000	25	6/9/2022	NON-COMPETING CONTINUATION	$469,424
														Subtotal = $469,424

Issue Date FY: 2021 ( Subtotal = $532,214 )
2021	2021	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	001	24	6/4/2021	SUPPLEMENT FOR EXPANSION	$53,210
2021	2021	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	000	24	6/3/2021	NON-COMPETING CONTINUATION	$479,004
														Subtotal = $532,214

Issue Date FY: 2020 ( Subtotal = $532,214 )
2020	2020	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	001	23	9/9/2020	SUPPLEMENT FOR EXPANSION	$53,210
2020	2020	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	000	23	6/26/2020	NON-COMPETING CONTINUATION	$479,004
														Subtotal = $532,214

Issue Date FY: 2019 ( Subtotal = $470,306 )
2019	2019	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	001	22	6/14/2019	NON-COMPETING CONTINUATION	$470,306
2019	2017	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD S	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	20	12/10/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $470,306

Issue Date FY: 2018 ( Subtotal = $479,004 )
2018	2018	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Biology Research	001	21	6/21/2018	COMPETING CONTINUATION	$479,004
2018	2017	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	20	6/15/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $479,004

Issue Date FY: 2017 ( Subtotal = $391,250 )
2017	2017	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	20	4/26/2017	NON-COMPETING CONTINUATION	$352,125
2017	2017	MAYO CLINIC JACKSONVILLE (A NONPROFIT CORPORATION)	4500 SAN PABLO RD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	001	20	6/7/2017	NON-COMPETING CONTINUATION	$39,125
														Subtotal = $391,250

Issue Date FY: 2016 ( Subtotal = $391,250 )
2016	2016	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	19	3/23/2016	EXTENSION WITH OR WITHOUT FUNDS	$391,250
														Subtotal = $391,250

Issue Date FY: 2015 ( Subtotal = $391,250 )
2015	2015	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	18	4/21/2015	NON-COMPETING CONTINUATION	$391,250
														Subtotal = $391,250

Issue Date FY: 2014 ( Subtotal = $379,513 )
2014	2014	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	17	4/8/2014	NON-COMPETING CONTINUATION	$379,513
														Subtotal = $379,513

Issue Date FY: 2013 ( Subtotal = $391,250 )
2013	2013	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	001	16	7/18/2013	COMPETING CONTINUATION	$391,250
2013	2012	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	15	7/12/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $391,250

Issue Date FY: 2012 ( Subtotal = $414,986 )
2012	2012	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	15	6/21/2012	NON-COMPETING CONTINUATION	$414,986
														Subtotal = $414,986

Issue Date FY: 2011 ( Subtotal = $417,869 )
2011	2011	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	14	6/23/2011	EXTENSION WITH OR WITHOUT FUNDS	$417,869
														Subtotal = $417,869

Issue Date FY: 2010 ( Subtotal = $438,109 )
2010	2010	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Trans-NIH Recovery Act Research Support	000	13	6/15/2010	NON-COMPETING CONTINUATION	$438,109
														Subtotal = $438,109

Issue Date FY: 2009 ( Subtotal = $430,738 )
2009	2009	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Trans-NIH Recovery Act Research Support	001	12	5/12/2009	COMPETING CONTINUATION	$430,738
2009	2008	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	11	5/12/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $430,738

Issue Date FY: 2008 ( Subtotal = $424,034 )
2008	2008	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	11	6/13/2008	NON-COMPETING CONTINUATION	$424,034
														Subtotal = $424,034

Issue Date FY: 2007 ( Subtotal = $422,576 )
2007	2007	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	10	5/7/2007	NON-COMPETING CONTINUATION	$422,576
														Subtotal = $422,576

Issue Date FY: 2006 ( Subtotal = $425,339 )
2006	2006	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	9	6/15/2006	NON-COMPETING CONTINUATION	$425,339
														Subtotal = $425,339

Issue Date FY: 2005 ( Subtotal = $425,775 )
2005	2005	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	8	9/13/2005	NON-COMPETING CONTINUATION	$425,775
														Subtotal = $425,775

Issue Date FY: 2004 ( Subtotal = $413,742 )
2004	2004	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	7	9/23/2004	COMPETING CONTINUATION	$413,742
														Subtotal = $413,742

Issue Date FY: 2003 ( Subtotal = $358,766 )
2003	2003	MAYO CLINIC JACKSONVILLE	4500 SAN PABLO ROAD	JACKSONVILLE	FL	32224	DUVAL	USA	Cancer Cause and Prevention Research	000	6	9/18/2003	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$313,794
2003	2003	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Cancer Cause and Prevention Research	000	5		NON-COMPETING CONTINUATION	$44,972
														Subtotal = $358,766

Grand Total All Awards = $9,860,608

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Protein Kinase C Signaling Mechanisms in Cancer

Award Number: R01CA081436

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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