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Targeting the Golgi Secretory Pathway in Chromosome 3q-amplified Human Cancer

Award Number: R01CA295608
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Targeting the Golgi Secretory Pathway in Chromosome 3q-amplified Human Cancer - PROJECT SUMMARY-ABSTRACT In contrast to the advancements made in non-small cell lung cancers (NSCLC) harboring actionable mutations in KRAS or receptor tyrosine kinases, few targeted therapies are available for NSCLCs lacking these mutations. A chromosome 3q (3q) region that is frequently amplified in NSCLC and other tumor types encodes several Golgi-resident proteins, including Golgi Integral Membrane Protein 4 (GOLIM4), which encodes a manganese (Mn)-binding Golgi scaffolding protein, and ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1), which encodes a Golgi-localized Ca2+/Mn2+ ion channel that mediates Ca2+-dependent cargo sorting and secretion. We found that the 3q amplicon plays a fundamental role in NSCLC progression owing to a Golgi-dependent secretory program activated by GOLIM4 and ATP2C1. Importantly, we show that Mn causes GOLIM4 degradation, thereby inducing a secretory blockade that leads to apoptosis of 3q-amplified, but not -diploid, NSCLC cells, suggesting that the 3q amplicon creates an addiction to the Golgi-dependent secretory program. In the proposed work, we will explore how a 3q amplicon activates secretory vesicle biogenesis in the Golgi to drive NSCLC progression, and we will carry out preclinical and mechanistic studies to elucidate how Mn selectively targets 3q-amplified NSCLC. Our studies will link somatic mutagenesis to a secretory process that drives NSCLC progression and will provide a molecular basis for future clinical studies of a metal as a targeted therapy in a genetically defined NSCLC subset.


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: 2026 ( Subtotal = $388,546 )
2026	2026	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	1	5/22/2026	NEW	$388,546
														Subtotal = $388,546

Grand Total All Awards = $388,546

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Targeting the Golgi Secretory Pathway in Chromosome 3q-amplified Human Cancer

Award Number: R01CA295608

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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