GOLM1 promotes hepatocellular carcinoma (HCC) metastasis by enhancing EGFR/RTK signaling.

  • Major finding: GOLM1 promotes hepatocellular carcinoma (HCC) metastasis by enhancing EGFR/RTK signaling.

  • Mechanism: GOLM1 promotes EGFR/RTK anchoring to the trans-Golgi network and recycling to the plasma membrane.

  • Impact: GOLM1 is linked to poor survival in patients with HCC and GOLM1 targeting may block metastasis.


Receptor tyrosine kinase (RTK) signaling can promote transformation and metastasis via multiple mechanisms, including defects in RTK endocytosis and recycling that increase RTK availability at the plasma membrane to enhance growth factor signaling. After RTKs are activated by ligand binding, they are internalized and undergo Golgi-mediated sorting leading to degradation or recycling, but it is unclear how the Golgi-related proteins that regulate these processes contribute to cancer and metastasis. Ye and colleagues found that the Golgi-related golgi membrane protein 1 (GOLM1) was upregulated in hepatocellular carcinoma (HCC) metastases compared to metastasis-free HCC and normal liver tissue. Further, in patients with HCC, high expression of GOLM1 was associated with early tumor recurrence and reduced overall survival. Consistent with these findings, GOLM1 depletion in HCC cell lines expressing high levels of GOLM1 reduced proliferation, migration, and invasion in vitro, and reduced tumor growth and lung metastases in tumor xenografts in vivo, indicating that GOLM1 promotes HCC growth and metastasis. GOLM1 regulates EGFR/RTK signaling by binding to activated and internalized EGFR, promoting EGFR recycling and return to the plasma membrane, and preventing EGFR degradation. The physical interaction between GOLM1 and EGFR was required for the GOLM1-mediated enhancement of cell migration, and GOLM1 mediated the polarized delivery of EGFR from the Golgi complex to the leading edge of HCC cells to promote migration and metastasis. The endosomal recycling compartment GTPase RAB11 is known to be involved in recycling RTKs from the trans-Golgi network to the plasma membrane, and GOLM1-mediated EGFR/RTK recycling was shown to require RAB11 with the GOLM1/RAB11/EGFR complex facilitating EGFR recycling to the plasma membrane. Collectively, these findings indicate that GOLM1 may promote metastasis in patients with HCC by regulation of EGFR/RTK recycling, and suggest that therapeutic targeting of GOLM1 may be a potential strategy for preventing metastasis in patients with HCC.

Ye QH, Zhu WW, Zhang JB, Qin Y, Lu M, Lin GL, et al. GOLM1 Modulates EGFR/RTK cell-surface recycling to drive hepatocellular carcinoma metastasis. Cancer Cell 2016;30:444–58.

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