TAGLN

Overview

TAGLN (transgelin, also known as SM22-alpha) is a smooth-muscle actin-binding protein that marks neural-crest-derived and mesenchymal cell lineages. In cancer genomics, TAGLN has emerged as a transcriptomic marker of the low-UV-burden (LowMut) subpopulation of normal melanocytes, which are characterized by neural-crest/stem-like gene expression programs distinct from the differentiated/pigmented high-UV-burden (HighMut) subpopulation.

Alterations observed in the corpus

  • TAGLN is transcriptionally upregulated in LowMut melanocytes (bottom UV-burden quartile) compared to HighMut melanocytes in a single-melanocyte multi-omics study (297 clonally-expanded cells, 31 donors); LowMut cells are enriched for smooth-muscle/neural-crest genes including TAGLN, MYL9, MYLK, SGCE, and HACD1 PMID:39975212.
  • TAGLN expression defines the neural-crest/stem-like transcriptional state of LowMut melanocytes, which carry predominantly clock-like SBS1/SBS5 mutational signatures rather than UV-attributable SBS7 PMID:39975212.
  • Mesenchymal-transition transcript up-regulated in pretreatment melanoma tumors that failed to respond to anti-PD-1 therapy; co-enriched within the IPRES (innate anti-PD-1 resistance) transcriptional signature PMID:26997480.

Cancer types (linked)

  • SKIN — TAGLN is a LowMut-state marker in normal cutaneous melanocytes from non-lesional skin adjacent to melanoma; no direct somatic driver role is established PMID:39975212.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • No drug targeting TAGLN is described in this corpus. The LowMut/neural-crest state marked by TAGLN is proposed as a reservoir of UV-protected melanocytes that could theoretically be leveraged for tissue rejuvenation, but no therapeutic intervention is validated PMID:39975212.

Open questions

  • Whether TAGLN-high (LowMut/stem-like) melanocytes are the cell-of-origin for melanoma subtypes with low UV-mutation burden remains untested PMID:39975212.
  • The causal direction of TAGLN expression in defining the LowMut niche vs. being a downstream consequence of follicular residence is not established PMID:39975212.

Sources

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