TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer.
The developmental transcription factor SOX4 contributes to the metastatic spread of multiple solid cancer types, but its direct target genes that mediate cancer progression are not well defined. Using a systematic molecular and genomic approach, we identified the TMEM2 transmembrane protein gene as a direct transcriptional target of SOX4. TMEM2 was transcriptionally activated by SOX4 in breast cancer cells where, like SOX4, TMEM2 was found to mediate proinvasive and promigratory effects. Similarly, TMEM2 was sufficient to promote metastatic colonization of breast cancer cells and its expression in primary breast tumors associated with a higher likelihood of metastatic relapse. Given earlier evidence that genetic inactivation of SOX4 or TMEM2 yield similar defects in cardiac development, our findings lead us to propose that TMEM2 may not only mediate the pathologic effects of SOX4 on cancer progression but also potentially its contributions to embryonic development. Cancer Res; 76(17); 4994-5005. ©2016 AACR.
Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York.
Hyeseung
H
Lee
Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York.
Hani
H
Goodarzi
Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York. stavazoie@mail.rockefeller.edu calarcon@mail.rockefeller.edu.
Sohail F
SF
Tavazoie
Laboratory of Systems Cancer Biology, Rockefeller University, New York, New York. stavazoie@mail.rockefeller.edu calarcon@mail.rockefeller.edu.
Claudio R
CR
Alarcón
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D055751:SOXC Transcription Factors / Q000235:genetics
C408224:CEMIP2 protein, human; D008565:Membrane Proteins; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors