title: HnRNPM and CD44s expression affects tumor aggressiveness and predicts poor prognosis in breast cancer with axillary lymph node metastases.
abstract: HnRNPM is an essential splicing factor and its expression is closely correlated with invasion and metastasis of tumor cells. The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and CD44 splice variants have been implicated in specific oncogenic signaling pathways. To investigate the clinical significance and biological function of hnRNPM, immunohistochemistry, quantitative, and semiquantitative polymerase chain reaction, lentiviral transfection system and transwell invasion assays were performed. We found that hnRNPM expression was significantly upregulated in breast cancer tissues compared with benign breast lesions. Although there was no significant correlation between hnRNPM and total CD44 protein or mRNA level, there was a negative correlation between hnRNPM and CD44v6. HnRNPM and CD44s expression showed positive correlation and in particular, they were dually expressed in breast cancer tissues. Interestingly, cancer stem cells marker, ALDH1+phenotype was positively associated with overexpression of CD44s or hnRNPM and negatively related to CD44v6. Patients with high hnRNPM tended to have higher levels of CD44s, shorter overall survival (OS) and higher rates of lymph node metastases (LNM). Remarkably, Kaplan-Meier and Cox regression analyses displayed that hnRNPM+or CD44shighwas a poor prognostic factor for OS of patients with LNM. Upregulation of hnRNPM in MCF-7 cells caused a significant increase in cell invasion, and this effect may occur through the regulation of CD44s expression. In conclusion, overexpression of hnRNPM promotes breast cancer aggressiveness by regulating the level of CD44s, indicates a poor prognosis for patients with LNM, and has potential as therapeutic targets.
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.
authors.forename: Huizhi
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, 300052, China.
authors.forename: Tieju
authors.identifier: 0000-0003-4522-545X
authors.initials: T
authors.lastname: Liu
authors.affiliation: Stomatology Hospital of Tianjin Medical University, China.
authors.forename: Dongwang
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, 300052, China.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, 300052, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.|Department of Pathology, General Hospital of Tianjin Medical University, 300052, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shao
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology, Tianjin Medical University, 300070, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D005260:Female; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C440104:HNRNPM protein, human; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D000444:Aldehyde Dehydrogenase