LGALS7

Galectin-7 (LGALS7) is a β-galactoside-binding lectin that operates both intracellularly and extracellularly to control lipid metabolism, cell proliferation, and tumor-associated immune modulation (PMID:34454908, PMID:36693903). In keratinocytes it physically binds HMGCS1 through phenylalanine 26 of HMGCS1 and upregulates HMGCS1 expression, raising cellular cholesterol levels in an interaction-dependent manner, with HMGCS1 in turn inducing Gal-7 to form a positive feedback loop (PMID:34454908). Gal-7 also amplifies its own abundance in cancer cells: extracellular Gal-7 drives autocrine transcriptional upregulation of the LGALS7 promoter and is taken up by endocytosis to re-enter cytosolic and mitochondrial compartments (PMID:29117220). In the tumor microenvironment, keratinocyte-overexpressed Gal-7 promotes non-melanoma skin carcinogenesis by binding CD11b+Ly6Chi monocytic myeloid cells and enhancing their immunosuppressive activity (IL-10 and TGF-β1 secretion, T-cell inhibition) downstream of c-Met activation and CXCL-1, an effect transferable by adoptive transfer of Gal-7-conditioned myeloid cells (PMID:36693903). Gal-7 additionally mediates Er:YAG laser-induced proliferation, migration, and invasion of periodontal ligament fibroblasts (PMID:32540310), and in gastric cancer it acts downstream of ANGPTL4 to engage Hedgehog signaling (PMID:39369030). Its expression is transcriptionally repressed in colorectal cancer by a METTL3/m6A-regulated ncRNA (PANC754)–PSPC1–H3K4me1 complex at the LGALS7 locus, limiting Gal-7-mediated immune evasion (PMID:40634299).

1. 2017 Medium

   Established that Gal-7 sustains its own levels, resolving how extracellular lectin influences intracellular pools by defining a self-amplification loop.

   Evidence Luciferase promoter reporter, mRNA quantification, and subcellular fractionation after recombinant Gal-7 treatment in breast and ovarian cancer lines

   PMID:29117220

   Open questions at the time

   • Endocytic receptor mediating Gal-7 re-entry not identified
   • Functional consequence of mitochondrial Gal-7 not defined
   • Single-lab cell-line evidence
2. 2020 Medium

   Showed Gal-7 is a required effector of laser-induced fibroblast responses, linking it to proliferation, migration, and invasion in periodontal tissue.

   Evidence Er:YAG laser irradiation of PDL fibroblasts with siRNA knockdown and proliferation/migration/invasion assays

   PMID:32540310

   Open questions at the time

   • Molecular partners downstream of Gal-7 in fibroblasts unknown
   • Mechanism coupling laser to LGALS7 transcription undefined
   • Single-lab knockdown only
3. 2021 High

   Identified a direct molecular partner and metabolic function, answering how Gal-7 promotes cholesterol accumulation in keratinocytes.

   Evidence Yeast two-hybrid, Biacore, co-IP, F26 site-directed mutagenesis, siRNA knockdown, and cholesterol quantification

   PMID:34454908

   Open questions at the time

   • Whether the HMGCS1 interaction depends on lectin carbohydrate-binding activity not resolved
   • Structural basis of F26 recognition not determined
   • Physiological/disease consequence of the cholesterol increase not tested
4. 2023 High

   Defined an in vivo immunomodulatory mechanism, establishing that Gal-7 drives skin carcinogenesis by reprogramming monocytic myeloid cells into immunosuppressors.

   Evidence Tg46 overexpression and Lgals7-/- mice in DMBA/TPA carcinogenesis with surface binding, myeloid depletion, and adoptive transfer epistasis

   PMID:36693903

   Open questions at the time

   • Myeloid surface receptor for Gal-7 not identified
   • Relationship between c-Met/CXCL-1 and direct Gal-7 binding not mechanistically dissected
   • Human relevance not tested
5. 2024 Medium

   Placed Gal-7 in a gastric cancer signaling axis, linking upstream ANGPTL4 to downstream Hedgehog pathway activity.

   Evidence RNA-seq, co-IP for ANGPTL4 interaction, functional assays, and nude mouse xenograft in AGS cells

   PMID:39369030

   Open questions at the time

   • Direct vs indirect ANGPTL4–LGALS7 interaction not distinguished
   • Mechanism by which LGALS7 engages Hedgehog signaling undefined
   • Apparent context-dependent anticancer vs pro-progression roles unreconciled
6. 2025 Medium

   Resolved how LGALS7 is silenced, defining an m6A/ncRNA/chromatin repression circuit that limits its immune-evasion function in colorectal cancer.

   Evidence PANC754 gain/loss-of-function, m6A/METTL3 analysis, PSPC1 binding, H3K4me1 chromatin assessment, and co-culture immune assays in vitro and in vivo

   PMID:40634299

   Open questions at the time

   • Direct PSPC1 occupancy at the LGALS7 locus vs docking prediction not fully validated
   • Mechanism of LGALS7-driven immune evasion not molecularly detailed
   • Single-lab model

• The molecular receptors and binding partners through which extracellular Gal-7 engages target cells (myeloid cells, fibroblasts) and unifies its metabolic, proliferative, and immunosuppressive roles remain undefined.
• No surface receptor identified for Gal-7 on myeloid or fibroblast targets
• No structural model of Gal-7 partner complexes
• Context-dependent pro- vs anti-tumor activity not reconciled across tissues