P-cadherin role in normal breast development and cancer

Albergaria, André; Ribeiro, Ana-Sofia; Vieira, André Filipe; Sousa, Bárbara; Nobre, Ana Rita; Seruca, Raquel; Schmitt, Fernando; Paredes, Joana

doi:10.1387/ijdb.113382aa

Cited by 68 publications

(78 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Р-кадгерин схож по строению с другими классическими кадгеринами и содержит три до-мена (внеклеточный, трансмембранный и внутриклеточ-ный), необходимых для осуществления гомофильных вза-имодействий. На клеточной мембране молекулы Р-кадгерина образуют латеральные димеры, которые вза-имодействуют по типу молнии, соединяя соседние клетки [43].…”

Section: р-кадгеринunclassified

“…Функция и сила Р-кадгеринассоциированной адгезии зависит от динамического взаимодействия с катенинами, которые связывают кадгериновый цитоплазматический конец с актиновым цитоскелетом и способствуют форми-рованию кадгерин-катениновых комплексов [43,44].…”

Section: р-кадгеринunclassified

“…Показано, что Е-и Р-кадгерин экспрессируются в эк-топлацентарном конусе, эктодерме, некоторых энтодер-мальных тканях и ткани почечного канальца, в то время как Р-и N-кадгерин экспрессируются во всех клетках ла-теральной пластинки мезодермы, эндотелии роговицы и радужной оболочке [43]. В тканях взрослого организма экспрессия Р-кадгерина обнаружена главным образом в базальном слое некоторых эпителиальных структур, таких как кожа, шейка матки, простата и легкие [43].…”

Section: р-кадгеринunclassified

“…В тканях взрослого организма экспрессия Р-кадгерина обнаружена главным образом в базальном слое некоторых эпителиальных структур, таких как кожа, шейка матки, простата и легкие [43].…”

Section: р-кадгеринunclassified

“…При раке молочной железы его избыточная продукция обнару-живается как при инвазивных карциномах, так и при про-токовых карциномах in situ [10,43]. Клинический интерес к Р-кадгерину появился несколько лет назад, когда группа ученых исследовала серию случаев карциномы легких и об-наружила, что Е-и Р-кадгерин коэкспрессировались в каж-дом из них.…”

Section: архив патологии 3 2015unclassified

See 4 more Smart Citations

Role of cadherins in health and in developing breast cancer

2015

View full text Add to dashboard Cite

Section: р-кадгеринunclassified

Section: архив патологии 3 2015unclassified

See 3 more Smart Citations

Role of cadherins in health and in developing breast cancer

2015

View full text Add to dashboard Cite

P‐cadherin functional role is dependent on E‐cadherin cellular context: a proof of concept using the breast cancer model

Ribeiro

Sousa

Carreto

et al. 2013

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

P-cadherin overexpression is associated with worse breast cancer survival, being a poor prognostic marker as well as a putative therapeutic target for the aggressive triple-negative and basal-like carcinomas (TNBCs). Previously, we have shown that P-cadherin promotes breast cancer invasion of cells where membrane E-cadherin was maintained; however, it suppresses invasion in models without endogenous cadherins, like melanomas. Here, we investigated if P-cadherin expression would interfere with the normal adhesion complex and which were the cellular/molecular consequences, constituting, in this way, a new mechanism by which E-cadherin invasive-suppressor function was disrupted. Using breast TNBC models, we demonstrated, for the first time, that P-cadherin co-localizes with E-cadherin, promoting cell invasion due to the disruption caused in the interaction between E-cadherin and cytoplasmic catenins. P-cadherin also induces cell migration and survival, modifying the expression profile of cells expressing wild-type E-cadherin and contributing to alter their cellular behaviour. Additionally, E- and P-cadherin co-expressing cells significantly enhanced in vivo tumour growth, compared with cells expressing only E- or only P-cadherin. Finally, we still found that co-expression of both molecules was significantly correlated with high-grade breast carcinomas, biologically aggressive, and with poor patient survival, being a strong prognostic factor in this disease. Our results show a role for E- and P-cadherin co-expression in breast cancer progression and highlight the potential benefit of targeting P-cadherin in the aggressive tumours expressing high levels of this protein.

show abstract

P‐Cadherin Is Coexpressed with CD44 and CD49f and Mediates Stem Cell Properties in Basal‐like Breast Cancer

et al. 2012

Self Cite

View full text Add to dashboard Cite

Although the luminal progenitor cell of the normal mammary gland hierarchy has been proposed as the cell-of-origin for basal-like breast cancers, finding the cancer stem cell (CSC) phenotype for this malignancy has proven a difficult task, mostly due to the lack of specific markers. Recently, basal-like sporadic and familial cases of breast cancer have been linked to BRCA1 gene inactivation, which enables the upregulation of the target-repressed CDH3/P-cadherin gene, an important biomarker of basallike breast carcinomas. Previously, we demonstrated that P-cadherin overexpression can mediate aggressive behavior in these tumors. Thus, our aim was to test whether P-cadherin mediates stem cell properties in basal-like breast carcinomas. Using a series of breast cancer cell lines and primary tumors, we showed that P-cadherin was directly associated with the expression of the breast stem markers CD44, CD49f, and aldehyde dehydrogenase 1 in the basal subtype. Moreover, cell population enriched for P-cadherin expression comprised increased in vitro mammosphere-forming efficiency and capacity to grow colonies in three-dimensional cultures as well as greater tumorigenicity. Importantly, an association was found with stem-/ progenitor-like phenotypes of the breast, including the luminal progenitor population, CD49f 1 CD24 1 . Additionally, P-cadherin expression conferred resistance to x-rayinduced cell death, sustaining a role for this molecule in another stem cell property. In summary, we demonstrated, for the first time, that P-cadherin mediates stem cell properties, which could be explored in order to better define the CSC phenotype of basal-like breast tumors and the cell-of-origin of this malignancy. STEM CELLS 2012;30:854-864 Disclosure of potential conflicts of interest is found at the end of this article.

show abstract

P-cadherin role in normal breast development and cancer

Cited by 68 publications

References 82 publications

Role of cadherins in health and in developing breast cancer

Role of cadherins in health and in developing breast cancer

P‐cadherin functional role is dependent on E‐cadherin cellular context: a proof of concept using the breast cancer model

P‐Cadherin Is Coexpressed with CD44 and CD49f and Mediates Stem Cell Properties in Basal‐like Breast Cancer

Contact Info

Product

Resources

About