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The CDCP1 Signaling Hub: A Target for Cancer Detection and Therapeutic Intervention

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CANCER RESEARCH
卷 81, 期 9, 页码 2259-2269

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AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-20-2978

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  1. National Health and Medical Research Council of Australia [APP1121970]
  2. Avner Pancreatic Cancer Foundation [R3 JH 2.1, APCF R5 2019]
  3. Medical Research Future Fund [MRF1199422]
  4. Mater Foundation
  5. Love Your Sister National Breast Cancer Foundation of Australia Fellowship
  6. University of Queensland Graduate School
  7. Tour de Cure [RSP-256-18/19]

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CDCP1 as an important hub for oncogenic signaling is upregulated in various malignancies and can be targeted for cancer diagnosis and therapy. Elevated levels of CDCP1 are associated with disease progression and poorer survival, predominantly located on the cell surface and involved in multiple cancer cell signaling pathways.
CUB-domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein that is upregulated in malignancies of the breast, lung, colorectum, ovary, kidney, liver, pancreas, and hematopoietic system. Here, we discuss CDCP1 as an important hub for oncogenic signaling and its key roles in malignant transformation and summarize approaches focused on exploiting it for cancer diagnosis and therapy. Elevated levels of CDCP1 are associated with progressive disease and markedly poorer survival. Predominantly located on the cell surface, CDCP1 lies at the nexus of key tumorigenic and metastatic signaling cascades, including the SRC/PKC delta, PI3K/AKT, WNT, and RAS/ERK axes, the oxidative pentose phosphate pathway, and fatty acid oxidation, making important functional contributions to cancer cell survival and growth, metastasis, and treatment resistance. These findings have stimulated the development of agents that target CDCP1 for detection and treatment of a range of cancers, and results from preclinical models suggest that these approaches could be efficacious and have manageable toxicity profiles.

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