CMTM8 As an LPA1-associated Partner Mediates Lysophosphatidic Acid-induced Pancreatic Cancer Metastasis

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2021 Feb 8

PMID 33553335

Citations 14

Authors

Weidong Shi

Chenyue Zhang

Zhouyu Ning

Yongqiang Hua

Ye Li

Lianyu Chen

Luming Liu

Zhen Chen

Zhiqiang Meng

Affiliations

Soon will be listed here.

Abstract

Background: Lysophosphatidic acid (LPA) is known to promote cancer cell invasiveness through LPA1, but the downstream signaling cascades are still not fully clarified. The CKLF-like MARVEL transmembrane domain-containing (CMTM) family regulates aggressive phenotype in many cancers.

Methods: We performed LPA1 co-immunoprecipitation combined with mass spectrometry to search for LPA1-associated proteins. The role of CMTM8 in mediating the pro-invasive activity of LPA was investigated in pancreatic cancer.

Results: We identified CMTM8 as an LPA1-interacting protein. LPA1 and CMTM8 were co-localized in pancreatic cancer cells. LPA treatment led to stabilization of CMTM8 protein, which was impaired by knockdown of LPA1. Depletion of CMTM8 significantly suppressed the migration and invasion of pancreatic cancer cells. Conversely, ectopic expression of CMTM8 enhanced the migratory and invasive capacity of pancreatic cancer cells. CMTM8 depletion blocked the formation of metastatic lesions in the lung. Knockdown of CMTM8 attenuated LPA-induced migration and invasion in pancreatic cancer cells. CMTM8 overexpression stimulated β-catenin activation through reduction of GSK3β. In addition, knockdown of β-catenin dramatically antagonized CMTM8-mediated migration and invasion in pancreatic cancer cells.

Conclusions: CMTM8 serves as a key mediator of LPA-induced invasiveness in pancreatic cancer. The interaction between CMTM8 and LPA1 leads to activation of oncogenic β-catenin signaling. CMTM8 represents a potential therapeutic target for pancreatic cancer.

Citing Articles

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Research insights into the chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM): their roles in various tumors.

Duan S, Jiang Y, Li G, Fu W, Song Z, Li L PeerJ. 2024; 12:e16757.

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