title: CD44 correlates with clinicopathological characteristics and is upregulated by EGFR in breast cancer.
abstract: Cluster of differentiation 44 (CD44), a well-known transmembrane glycoprotein, serves as a promoting factor in the carcinogenesis and progression of a variety of neoplasms. Previous studies have demonstrated that aberrant expression of CD44 was associated with the initiation, invasion, metastasis, and therapy-resistance of breast cancer, but whether there was any association between CD44 and pathological characteristics of breast cancer or epidermal growth factor receptor (EGFR) has not been clearly elucidated. In this study, we utilized public microarray data analysis and tissue microarray technologies to display that CD44 level was enhanced in breast cancer and was significantly correlated with histological grade and the status of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 (HER2) and EGFR. Furthermore, mRNA expression of CD44 in breast tumors was positively correlated with basal cytokeratin markers KRT5 and KRT17, but inversely associated with luminal marker FOXA1. Besides, Kaplan-Meier analysis showed that high CD44 mRNA level had adverse impact on the progression-free survival of patients with HER2-expressing or basal-like breast cancer. Functionally, inhibition of EGFR activity by erlotinib impaired the invasion and migration ability of breast cancer cell lines. Western blot assays demonstrated that erlotinib treatment decreased the expression of CD44, accompanied with the reduced protein levels of mesenchymal and cancer stem cell markers. Collectively, this study suggested that the expression of CD44 was upregulated by EGFR pathway and CD44 had a robust impact on the development of breast cancer.
authors: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors: Hanxiao
authors: H
authors: Xu
authors: Nursing School of Pingdingshan University, Pingdingshan, Henan 467000, P.R. China.
authors: Kongju
authors: K
authors: Wu
authors: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors: Yijun
authors: Y
authors: Tian
authors: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors: Qian
authors: Q
authors: Liu
authors: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors: Na
authors: N
authors: Han
authors: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors: Xun
authors: X
authors: Yuan
authors: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors: Lu
authors: L
authors: Zhang
authors: Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors: Gen Sheng
authors: GS
authors: Wu
authors: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors: Kongming
authors: K
authors: Wu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism*; D053555:Keratin-5 / Q000235:genetics; D007633:Keratins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: C497483:CD44 protein, human; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D018960:Hyaluronan Receptors; C503940:KRT5 protein, human; D053555:Keratin-5; D007633:Keratins; C512478:EGFR protein, human; D066246:ErbB Receptors