Affinage

FAM135A

Protein FAM135A · UniProt Q9P2D6

Length
1515 aa
Mass
169.8 kDa
Annotated
2026-06-09
11 papers in source corpus 1 papers cited in narrative 4 extracted findings
Cross-family judge faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FAM135A is a signaling-responsive transcriptional regulator that drives perineural invasion in prostate cancer (PMID:41250119). Its expression is activated downstream of the GRP→GRPR signaling axis, and pharmacological GRPR inhibition represses FAM135A through MED15 activation (PMID:41250119). The nuclear transporter RAN mediates cytoplasmic-to-nuclear translocation of FAM135A, generating a nuclear-enriched form (nFAM135A) that acts as a transcriptional activator of TENM3, a target required for cancer-nerve invasion (PMID:41250119). Loss of FAM135A abrogates tumor malignancy and neural invasion in both AR-positive and AR-negative prostate cancer cells and limits tumor growth while improving motor function in a sciatic-nerve invasion mouse model (PMID:41250119). Beyond this prostate cancer perineural-invasion axis, no further biochemical or structural detail for FAM135A has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2025 Medium

    Established that FAM135A is a downstream effector of GRPR signaling in prostate cancer, placing it within a defined upstream pathway rather than as an isolated factor.

    Evidence RNA-seq, ChIP-seq, and GRPR pharmacological inhibition with FAM135A silencing in prostate cancer cells

    PMID:41250119

    Open questions at the time
    • Direct mechanism by which GRPR signaling and MED15 control FAM135A transcription not resolved
    • Whether FAM135A activation occurs in non-prostate contexts unknown
  2. 2025 Medium

    Identified RAN-mediated nuclear translocation as the step that converts cytoplasmic FAM135A into a transcriptionally active nuclear pool, defining how its activity is spatially controlled.

    Evidence Subcellular fractionation/localization experiments identifying RAN as the transporter in prostate cancer cells

    PMID:41250119

    Open questions at the time
    • Nuclear localization signal or direct RAN-FAM135A interaction not biochemically defined
    • Signal triggering translocation not established
  3. 2025 Medium

    Showed that nuclear FAM135A functions as a transcriptional regulator of TENM3, providing the downstream gene required for its pro-invasive effect.

    Evidence ChIP-seq target identification, RNA-seq, and rescue/silencing experiments in prostate cancer cells

    PMID:41250119

    Open questions at the time
    • Whether FAM135A binds DNA directly or acts via a co-regulator not determined
    • Full target gene set beyond TENM3 not delineated
  4. 2025 Medium

    Demonstrated functional requirement for FAM135A in tumor malignancy and neural invasion across androgen-receptor states, linking the molecular pathway to in vivo disease phenotypes.

    Evidence FAM135A silencing in AR-positive and AR-negative cells, co-culture perineural invasion assay, and in vivo sciatic-nerve invasion mouse model

    PMID:41250119

    Open questions at the time
    • All evidence from a single lab and single study
    • Therapeutic targetability not tested directly

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intrinsic biochemical activity of FAM135A and its mechanism of DNA/chromatin engagement remain undefined.
  • No structural model or enzymatic activity characterized
  • No reciprocal validation of the RAN interaction
  • Function outside prostate cancer unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
RAN

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 FAM135A is activated downstream of the GRPR signaling axis (GRP→GRPR→FAM135A) in prostate cancer cells; pharmacological GRPR inhibition represses FAM135A expression via MED15 activation. RNA-seq, ChIP-seq, in vitro co-culture perineural invasion assay, in vivo sciatic-nerve invasion mouse model, FAM135A silencing (loss-of-function) Molecular cancer Medium 41250119
2025 FAM135A undergoes cytoplasmic-to-nuclear translocation mediated by the nuclear transporter protein RAN, resulting in nuclear-enriched FAM135A (nFAM135A). Subcellular fractionation/localization experiments and mechanistic follow-up identifying RAN as the transporter Molecular cancer Medium 41250119
2025 Nuclear FAM135A (nFAM135A) acts as a transcriptional regulator that drives expression of Teneurin Transmembrane Protein 3 (TENM3), which is required for nFAM135A-induced cancer-nerve invasion. ChIP-seq (identifying TENM3 as a transcriptional target), RNA-seq, and functional rescue/silencing experiments in prostate cancer cells Molecular cancer Medium 41250119
2025 FAM135A silencing abrogates tumor malignancy and neural invasion in vitro (in AR-positive LNCaP and AR-negative DU145/PC3 cells) and controls tumor growth and improves motor function in an in vivo PCa-sciatic nerve invasion mouse model. Loss-of-function (FAM135A silencing) in co-culture perineural invasion assay and in vivo sciatic-nerve invasion mouse model Molecular cancer Medium 41250119

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 LncRNA MIR17HG Suppresses Breast Cancer Proliferation and Migration as ceRNA to Target FAM135A by Sponging miR-454-3p. Molecular biotechnology 25 36943627
2022 Establishment and characterization of the third non-functional human pancreatic neuroendocrine tumor cell line. Human cell 13 35394261
2015 Identification of candidate genes that underlie the QTL on chromosome 1 that mediates genetic differences in stress-ethanol interactions. Physiological genomics 13 25991709
2019 Construction of miRNA-target networks using microRNA profiles of CVB3-infected HeLa cells. Scientific reports 11 31784561
2005 Exclusion of four candidate genes, KHDRBS2, PTP4A1, KIAA1411 and OGFRL1, as causative of autosomal recessive retinitis pigmentosa. Ophthalmic research 9 16192744
2024 Genomic basis of melanin-associated phenotypes suggests colour-specific environmental adaptations in tawny owls. Molecular ecology 6 38173194
2024 Differential Expression of MicroRNA MiR-145 and MiR-155 Downstream Targets in Oral Cancers Exhibiting Limited Chemotherapy Resistance. International journal of molecular sciences 5 38396844
2023 Deciphering novel common gene signatures for rheumatoid arthritis and systemic lupus erythematosus by integrative analysis of transcriptomic profiles. PloS one 4 36928613
2025 GRPR-induced FAM135A expression promote perineural invasion in prostate cancer. Molecular cancer 1 41250119
2026 Ethnic-specific effects of the LILRB2-LILRB5 locus and newly identified risk loci for Alzheimer's disease in the East Asian population. Alzheimer's & dementia : the journal of the Alzheimer's Association 0 41700061
2026 Whole-Genome Resequencing Reveals Population Structure and Loci Associated with Growth and Meat-Quality Traits in Meigu Yanying Chickens. Animals : an open access journal from MDPI 0 41751003

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