title: Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity.
abstract: Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite to metastasis, and monocarboxylate transporter 1 (MCT1). MCT1 transporter activity is known to regulate aspects of tumor progression and, as such, is a clinically relevant target for treating cancer. Knockdown of MCT1 expression caused decreased hepatocyte growth factor (HGF)-induced as well as epidermal growth factor (EGF)-induced tumor cell scattering and wound healing. Western blot analysis suggested that MCT1 knockdown (KD) hinders signaling through the HGF receptor (c-Met) but not the EGF receptor. Exogenous, membrane-permeable MCT1 substrates were not able to rescue motility in MCT1 KD cells, nor was pharmacologic inhibition of MCT1 able to recapitulate decreased cell motility as seen with MCT1 KD cells, indicating transporter activity of MCT1 was dispensable for EGF- and HGF-induced motility. These results indicate MCT1 expression, independent of transporter activity, is required for growth factor-induced tumor cell motility. The findings presented herein suggest a novel function for MCT1 in tumor progression independent of its role as a monocarboxylate transporter.
authors.affiliation: Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.|Feist-Weiller Cancer Center, Shreveport, LA, USA.
authors.forename: Alana L
authors.initials: AL
authors.lastname: Gray
authors.affiliation: Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.|Feist-Weiller Cancer Center, Shreveport, LA, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Coleman
authors.affiliation: Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.|Feist-Weiller Cancer Center, Shreveport, LA, USA.
authors.forename: Runhua
authors.initials: R
authors.lastname: Shi
authors.affiliation: Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.|Feist-Weiller Cancer Center, Shreveport, LA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Cardelli
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D019859:Proto-Oncogene Proteins c-met; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C491743:MET protein, human
keywords: EGF; HGF; MCT1; cancer; motility