title: Involvement of nuclear NHERF1 in colorectal cancer progression.
abstract: NHERF1 (Na+/H+ exchanger regulatory factor 1) is expressed in the luminal             membrane of many epithelia, and associated with proteins involved in tumor progression.             Alterations of NHERF1 expression in different sites of metastatic colorectal cancer             (mCRC) suggest a dynamic role of this protein in colon carcinogenesis. We focused             on the observation of the altered expression of NHERF1 from non-neoplastic tissues             to metastatic sites by immunohistochemistry. Moreover, we studied, by immunofluorescence,             the colocalization between NHERF1 and the epidermal growth factor receptor (EGFR),             whose overexpression is implicated in CRC progression. NHERF1 showed a different             localization and expression in the examined sites. The distant non-neoplastic             tissues showed NHERF1 mostly expressed at the apical membrane, while in surrounding             non-neoplastic tissue decreased the apical membrane and increased cytoplasmic             immunoreactivity. In adenomas a shift from apical membrane to cytoplasmic localization             and nuclear expression were observed. Cytoplasmic staining in the tumor, and metastatic             sites was stronger than surrounding non-neoplastic tissue. Furthermore, nuclear             NHERF1 expression was noted in 80% of all samples and surprisingly, it appeared             already in adenoma lesions, suggesting that NHERF1 represents an early marker             of pre-morphological triggering of colorectal carcinogenesis. Then, in few tumors             a positive direct correlation between membrane NHERF1 and EGFR expression was             evidenced by their colocalization. Nuclear NHERF1 expression, present in the early             stages of carcinogenesis and related with poor prognosis, may contribute to the             onset of malignant phenotype. Specifically, we hypothesize the direct involvement             of nuclear NHERF1 in both carcinogenesis and progression and its role as a potential             colorectal cancer marker.
authors: Functional Biomorphology Laboratory, Department of Pathology, National Cancer Centre, Bari, Italy. a.mangia@oncologico.bari.it
authors: Anita
authors: A
authors: Mangia
authors: Concetta
authors: C
authors: Saponaro
authors: Andrea
authors: A
authors: Malfettone
authors: Domenico
authors: D
authors: Bisceglie
authors: Antonia
authors: A
authors: Bellizzi
authors: Mariaconsilia
authors: M
authors: Asselti
authors: Ondina
authors: O
authors: Popescu
authors: Stephan J
authors: SJ
authors: Reshkin
authors: Angelo
authors: A
authors: Paradiso
authors: Giovanni
authors: G
authors: Simone
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D066246:ErbB Receptors