PARVA

PARVA (α-parvin) functions as a pro-invasive scaffold that drives tumor cell invasion and metastasis through an ILK-dependent signaling axis (PMID:25738875). PARVA forms a complex with SGK1 and ILK, and its overexpression enhances ILK phosphorylation, leading to downstream Akt phosphorylation and inhibition of GSK3β; pharmacological inactivation of ILK reverses PARVA-induced invasion, placing PARVA upstream of ILK in this axis (PMID:25738875). PARVA expression is post-transcriptionally restrained by the A-to-I edited form of miR-378a-3p, which preferentially binds the PARVA 3'-UTR—unlike the unedited miRNA—thereby suppressing melanoma metastasis and linking RNA editing to PARVA-dependent progression (PMID:29386624). Beyond these two findings, no further mechanistic detail has been characterized in the available corpus.

1. 2015 Medium

   Established that PARVA acts upstream of ILK in a pro-invasive signaling cascade rather than merely correlating with invasion, defining a concrete molecular axis for its phenotypic effects.

   Evidence Reciprocal Co-IP demonstrating a PARVA-SGK1-ILK complex, combined with siRNA knockdown, overexpression, invasion/colony/tube-formation assays, in vivo metastasis models, and ILK inhibitor rescue

   PMID:25738875

   Open questions at the time

   • Stoichiometry and direct binding interfaces of the PARVA-SGK1-ILK complex not resolved
   • Whether the effect generalizes beyond the cancer models tested is unaddressed
   • Mechanism by which PARVA enhances ILK phosphorylation (direct vs. scaffolding) not defined
2. 2018 Medium

   Identified how PARVA expression is controlled, showing that A-to-I RNA editing redirects miR-378a-3p to target PARVA and thereby suppress metastasis, connecting an upstream regulatory layer to PARVA-driven progression.

   Evidence 3'-UTR luciferase reporter assay with edited vs. wild-type miR-378a-3p, qRT-PCR/Western blot of PARVA in metastatic vs. non-metastatic melanoma cells, and an in vivo melanoma metastasis mouse model

   PMID:29386624

   Open questions at the time

   • Editing enzyme responsible for generating the active miR-378a-3p not characterized in this entry
   • Whether PARVA is the sole functionally relevant target of the edited miRNA is not established
   • Quantitative contribution of PARVA repression to the overall metastatic phenotype unresolved

• The structural basis of PARVA's scaffolding within the ILK complex and the breadth of its functions outside the melanoma/invasion context remain unknown.
• No structural model of the PARVA-SGK1-ILK complex
• No subcellular localization data in the corpus
• Functions of PARVA outside tumor invasion not examined