Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells

Salaria, Safia N.; Illei, Peter B.; Sharma, Rajni; Walter, Kimberly; Klein, Alison P.; Eshleman, James R.; Maitra, Anirban; Schulick, Richard D.; Winter, Jordan M.; Ouellette, Michel; Goggins, Michael; Hruban, Ralph H.

doi:10.4161/cbt.6.3.3904

Cited by 49 publications

(48 citation statements)

References 25 publications

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“…Serial analysis of gene expression (SAGE) of pancreatic and colorectal cancers at invasive sites, comprising both epithelial and stromal elements, identified palladin to be within a cluster of invasion-specific genes (63). However, in a separate report by Salaria et al, it was found that palladin expression levels were comparable between pancreatic cancer cells and non-neoplastic pancreatic cells, with high expression levels predominantly seen in non-neoplastic stromal fibroblasts of pancreatic tumor sections (64). These previous reports showing an up-regulation of palladin with increased invasion is invariant to our observation that loss in palladin expression is associated with increased invasiveness in colon rectal cancer.…”

Section: Discussionsupporting

confidence: 86%

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells

Tay

Tan²,

Lan³

et al. 2010

Int J Oncol

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Abstract. Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchymal transition) features showed a down-regulation of palladin gene expression in the latter. Knockdown of palladin expression in the HCT116 cells suppressed junctional localization of E-cadherin, reduced intercellular adhesion and collective cell migration, showing that palladin plays an important role in maintaining the integrity of adherens junctions. The acquisition of the EMT features by the E1 cell line was dependent on the Erk pathway. Inhibition of this pathway by U0126 treatment in E1 cells resulted in the re-expression of palladin, relocalization of E-cadherin to the adherens junctions and a reversal of EMT features. The re-establishment of intercellular adhesion was dependent on palladin expression. The down-regulation of palladin was also observed in poorly-differentiated tumor tubules and dissociated tumor cells that have undergone de-differentiation in human primary colon tumors. Our data show that palladin is an integral component of adherens junctions and plays a role in the localization of E-cadherin to the junctions. The loss of palladin may be an integral part of EMT, an early step in the metastatic spread of colon carcinoma.

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Section: Discussionsupporting

confidence: 86%

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells

Tay

Tan²,

Lan³

et al. 2010

Int J Oncol

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“…Recently, Brentnall et al have identified a germ line mutation in the PALLD gene on chromosome 4q32-34 in Family X, a family with a unusual phenotype of early-onset pancreatic insufficiency, diabetes mellitus, and familial pancreatic cancer typically before age 40 (12). This locus does not seem to be a site of linkage in most pancreatic cancer families (13,14), although additional mutational studies of PALLD in other kindreds are awaited (15).…”

mentioning

confidence: 99%

“…Stromal contamination and small samples are significant challenges when studying any pancreatic neoplasm (26). Careful laser capture microdissection (LCM) of neoplastic cells can prevent contamination by the abundant stromal reaction associated with the infiltrating cancer cells, and whole genome amplification (WGA) techniques can accurately copy small starting amounts of DNA, thereby enabling the detailed analysis of DNA available from LCM tissues (27).…”

mentioning

confidence: 99%

Genome-Wide Allelotypes of Familial Pancreatic Adenocarcinomas and Familial and Sporadic Intraductal Papillary Mucinous Neoplasms

Abe¹,

Fukushima²,

Brune³

et al. 2007

Clinical Cancer Research

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Purpose: Most familial cancer susceptibility genes are tumor suppressor genes that are biallelically inactivated in familial neoplasms through somatic deletion of the wild-type allele. Identifying the genomic losses that occur in pancreatic neoplasms, particularly those that occur in familial and precursor neoplasms, may help localize the genes responsible for pancreatic cancer susceptibility. Experimental Design: Normal and neoplastic tissue DNA was isolated from fresh-frozen surgically resected tissues from 20 patients with primary familial pancreatic adenocarcinoma (defined as having at least one first-degree relative with pancreatic cancer), 31 with sporadic intraductal papillary mucinous neoplasms (IPMN), and 7 with familial IPMNs using laser capture microdissection. Microdissected DNA was whole genome amplified using multiple strand displacement. Genome-wide allelotypes were determined using 391 microsatellite markers. The accuracy of microdissection and fidelity of the whole genome amplification were determined by comparing the genotypes of microdissected primary pancreatic cancers to the genotypes of xenografts derived from these cancers and by comparing the results of amplified to nonamplified specimens. Results: The concordance of genotypes between LCM whole genome amplified primary pancreatic cancers and their corresponding pancreatic cancer xenograft DNAs was 98%. Among the 20 primary familial pancreatic adenocarcinomas, we found a high prevalence of loss of heterozygosity (LOH) with an average fractional allelic loss (FAL) of 49.9% of an aggregate of 2,378 informative markers. The level of FAL in the IPMNs (10%) was significantly lower than in the pancreatic adenocarcinomas. The most common locus of LOH in the IPMNs was at 19p (LOH at 24% of markers). The regions of frequent allelic loss observed in the familial pancreatic cancers were similar to those found in sporadic pancreatic cancers. Conclusions:The allelic loss patterns of familial and sporadic pancreatic cancers and IPMNs provide clues as to the genomic locations of tumor suppressor genes inactivated in these neoplasms.

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“…Les études des expressions des gènes montrent une surexpression de ce gène au cours de la carcinogenèse pancréatique [55]. Cependant, les études ultérieures n'ont pas confirmé l'implication de ce gène dans le cancer pancréa-tique familial [56][57][58][59][60].…”

Section: Gène Paladin (Palld)unclassified

Pancreatic cancer and genetics

Boumendjel

2015

Oncologie

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Le cancer du pancréas est un cancer relativement rare, mais au pronostic très sombre. Le rapport incidence/ décès est de 0,99. Le taux de survie à cinq ans, tous stades confondus, est l'un des plus bas, il est d'environ 5 % en Europe comme aux États-Unis. Donc, c'est très préoccupant en matière de santé publique. Le dépistage du cancer pancréatique permettant un diagnostic précoce de la maladie, et donc augmentant les chances de traitement curatif, n'existe pas. Le cancer pancréatique est dans la plupart des cas sporadique. Néanmoins, il existe des formes familiales de cette affection tumorale qui sont responsables d'une proportion importante, plus de 10 % des cas leur sont imputables. Dans cette revue, on s'est focalisé sur la génétique du cancer pancréatique, particulièrement le cancer pancréatique survenant dans un contexte familial. Mots clés Cancer pancréatique · GénétiqueAbstract Pancreatic cancer, although relatively rare, does have a very poor prognosis. The ratio of incidence to deaths is 0.99. The survival rate at five years from all stages is one of the lowest, at around 5% in both Europe and the USA. It is therefore a serious public health issue. Screening for pancreatic cancer, which would enable an early diagnosis to be made and thus increase the chances of being cured, does not exist. In the majority of cases, pancreatic cancer is sporadic. However, there are familial forms of this disease, which are responsible for a significant proportion of cases, with more than 10% of cases being attributable to this type. In this review, focus is on the genetics of pancreatic cancer, in particular pancreatic cancer occurring within the same family.

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Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells

Cited by 49 publications

References 25 publications

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells

Genome-Wide Allelotypes of Familial Pancreatic Adenocarcinomas and Familial and Sporadic Intraductal Papillary Mucinous Neoplasms

Pancreatic cancer and genetics

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