Non-Canonical Function of the Golgi Tethering Factor Golgin-97 in the Regulation of Cancer Invasiveness

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


It has been increasingly clear that the Golgi apparatus functions in several biological processes, including vesicle trafficking, cytoskeletal dynamics, receptor signaling, autophagocytosis, and mitosis. Golgin-97, a Golgi tethering factor, has roles in the regulation of vesicle transport at the trans-Golgi network (TGN) and the Golgi architecture maintenance. Recently, we identified a novel role of golgin-97 in the suppression of cancer cell invasiveness. We found that low expression of golgin-97 correlates with the poor overall survival of cancer patients and breast cancer cell invasiveness. Interestingly, we also found that golgin-97 can suppress NF-κB-mediated cell mobility, but this act does not depend on its function on retrograde transport form endosome to TGN or Golgi structure maintenance (Cell Commun. Signal. 2018). This study reveals an non-canonical function of golgin-97 in the suppression of signaling required for cancer invasiveness. However, the underlying mechanisms remain unclear. In this proposal, we aim to investigate the molecular mechanisms of golgin-97 in the regulation of cancer metastasis in vitro and in vivo. Our preliminary data show that (1) several NF-κB regulators were identified as golgin-97-interating proteins; (2) critical kinase cascades responded to golgin-97 knockdown were identified by phosphoproteomics approaches; (3) the golgin-97-regulated secreted proteins is involved in tumor-promoting inflammation; (4) the hypoxia might be involved in regulation of golgin-97 expression; (5) increased migration ability and reduced IκB level were observed in golgin-97 CRISPR knockout breast cancer cells. The objective of this proposal is to explore the fundamental basis of the non-canonical role of golgin-97 in cancer metastasis which may be allowed to develop novel targets for cancer treatments. Our specific aims include: 1. To identify and characterize golgin-97-interacting proteins, which are involved in suppressing the NF-κB activity. 2. To identify and characterize the upstream regulators of golgin-97 involved in cancer cell invasiveness. 3. To examine in vivo function of golgin-97 in cancer metastasis and inflammation using xenograft mouse model. The expected impact on social and academic development after the implementation of this project include: (1) it provides the knowledge of the non-canonical function of golgin-97 in cancer metastasis; (2) it provides the integrated omics and bioinformatics approaches to study the underlying mechanisms of golgin-97 in cancer cell invasiveness; (3) it provides the basis to develop therapeutic targets of cancers by modulating the golgin-97 expression and its downstream effectors.

Project IDs

Project ID:PC10901-2007
External Project ID:MOST108-2320-B182-007-MY3
Effective start/end date01/08/2031/07/21


  • Golgi
  • golgin-97
  • tumor suppressor
  • invasiveness
  • metastasis
  • phosphoproteome
  • signaling


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.