Paradoxical downregulation of LPAR3 exerts tumor-promoting activity through autophagy induction in Ras-transformed cells.

ABSTRACT:

Background

Lysophosphatidic acid receptor 3 (LPAR3) is coupled to Gα_i/o and Gα_11/q signaling. Previously, we reported that LPAR3 is highly methylated in carcinogen-induced transformed cells. Here, we demonstrate that LPAR3 exhibits malignant transforming activities, despite being downregulated in transformed cells.

Methods

The LPAR3 knockout (KO) in NIH 3 T3 and Bhas 42 cells was established using the CRISPR/Cas9 system. Both RT-PCR and DNA sequencing were performed to confirm the KO of LPAR3. The cellular effects of LPAR3 KO were further examined by WST-1 assay, immunoblotting analysis, transwell migration assay, colony formation assay, wound scratch assday, in vitro cell transformation assay, and autophagy assay.

Results

In v-H-ras-transformed

SUBMITTER: Hwang SH 

PROVIDER: S-EPMC9463806 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature