Integrin beta-like protein 1 (ITGBL1)

ITGBL1 (Integrin beta-like protein 1) is an extracellular matrix protein found in high concentrations within extracellular vesicles released from metastatic cancer cells. These ITGBL1-rich EVs interact with fibroblasts at distant sites, activating pro-inflammatory signaling (notably the NF-κB pathway) and facilitating the formation of a pre-metastatic supportive environment (niche) which aids metastatic tumor growth. ITGBL1 also acts in cancer cells to stimulate TGF-β/Smads signaling, promoting cell migration and invasion. High ITGBL1 levels in tumors or bodily fluids are associated with poor prognosis, cancer metastasis, and liver fibrosis progression. While ITGBL1 itself is not a classic receptor or enzyme, its pivotal role in EV-mediated tumor-stromal interactions and disease progression makes it a potential therapeutic and diagnostic target.

Other names

Integrin, beta-like 1ITGBL1TIED (Tenascin-X inter-alpha-trypsin inhibitor heavy chain–related extracellular matrix protein)

Inhibition or targeting of ITGBL1 could disrupt the formation and pro-metastatic function of ITGBL1-containing EVs, prevent NF-κB activation in fibroblasts, and diminish pre-metastatic niche formation. Targeting downstream pathways (such as TGF-β/Smads or NF-κB) activated by ITGBL1-evoked EV signaling.