Chromosome 1 Open Reading Frame 35 Drives Colorectal Cancer Progression by Enhancing Tumor-Intrinsic Proliferation...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Immunology

Background:

• The role of Chromosome 1 open reading frame 35 (C1orf35) in colorectal cancer (CRC) is not well understood.
• Investigating C1orf35 is crucial for identifying new therapeutic strategies for CRC.

Purpose of the Study:

• To elucidate the functional significance and oncogenic mechanisms of C1orf35 in colorectal cancer.
• To determine C1orf35's impact on tumor growth and the tumor immune microenvironment.

Main Methods:

• Analysis of C1orf35 expression in CRC clinical specimens.
• Functional assays using patient-derived organoids.
• Investigation of molecular mechanisms involving c-Myc and pyrroline-5-carboxylate reductase 2 (PYCR2).
• Assessment of C1orf35's effect on CD8+ T cell function and infiltration using multiplex immunohistochemistry.

Main Results:

• C1orf35 is frequently upregulated in CRC and correlates with advanced stage and poor survival.
• C1orf35 drives CRC cell proliferation, migration, and expansion.
• C1orf35 activates c-Myc, leading to PYCR2 upregulation and enhanced tumor growth.
• C1orf35 suppresses CD8+ T cell cytotoxic function and infiltration, creating an immune-suppressive tumor microenvironment.

Conclusions:

• C1orf35 is a dual-function oncoprotein promoting CRC progression through intrinsic growth and immune suppression.
• The c-Myc/PYCR2 axis is a key mechanism for C1orf35-mediated tumor growth.
• C1orf35 represents a promising prognostic biomarker and therapeutic target for colorectal cancer.