# Lysophosphatidic acid down-regulates human RIPK4 mRNA in keratinocyte- derived cell lines

## TL;DR

This study shows that lysophosphatidic acid reduces RIPK4 mRNA in skin cells, which may contribute to skin cancer progression.

## Contribution

The novel finding is that lysophosphatidic acid inhibits RIPK4 transcription, linking it to keratinocyte proliferation and cancer.

## Key findings

- Lysophosphatidic acid down-regulates RIPK4 mRNA transcription in keratinocyte-derived cell lines.
- Reduced RIPK4 expression compromises increased keratinocyte proliferation caused by lysophosphatidic acid.
- The study provides insights into RIPK4 downregulation during squamous cell carcinoma progression.

## Abstract

The tight control of proliferating keratinocytes is vital to the successful function of the skin. Differentiation of dividing cells is necessary to form a skin barrier. The same dividing cells are necessary to heal wounds and when malignant form tumors. RIPK4, a serine-threonine kinase, plays critical roles in these processes. Its loss of function was associated with pathological keratinocyte proliferation and development of squamous cell carcinoma (SCC) in humans and mice. The current study extends previous findings in the importance of RIPK4 in keratinocyte proliferation. A serum-derived phospholipid, lysophosphatidic acid (LPA), was identified as an important biologic inhibitor of RIPK4. LPA functions by inhibiting the transcription of RIPK4 mRNA. LPA treatment led to increased keratinocyte proliferation, and this was compromised in cells with reduced RIPK4 expression. The current study may help to explain the mechanism by which RIPK4 was downregulated during SCC progression and provide insights on RIPK4 functions. It may also allow for targeting of RIPK4 through a natural component of serum.