Genetic alterations of epithelial polarity genes are associated with loss of polarity in invasive breast cancer

Catterall, Rachel; Lelarge, Virginie; McCaffrey, Luke

doi:10.1002/ijc.32691

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…Partial or complete inversion of local polarity is associated with microvillus inclusion disease (Michaux et al, 2016), and pathogenic bacteria can appropriate local apico-basolateral polarity programs in the intestine, disrupting barrier function and providing bacteria access to internal compartments (Hua et al, 2018; Tapia et al, 2017a; Tapia et al, 2017b). Loss of global, tissue-level polarity results in non-adherent cells that disassociate or fail to undergo morphogenic movements, resulting in embryonic lethality (Achilleos et al, 2010; Bilder et al, 2000; Bossinger et al, 2001; Hutterer et al, 2004; Legouis et al, 2000; McMahon et al, 2001; Totong et al, 2007) or that promote the progression and metastasis of cancers (Catterall et al, 2020; Ellenbroek et al, 2012; Halaoui et al, 2017; Zhou et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Separable mechanisms drive local and global polarity establishment in the C. elegans intestinal epithelium

Pickett

Sallee

et al. 2021

Preprint

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Apico-basolateral polarization is essential for epithelial cells to function as selective barriers and transporters, and to provide mechanical resiliency to organs. Epithelial polarity is established locally, within individual cells to establish distinct apical, junctional, and basolateral domains, and globally, within a tissue where cells coordinately orient their apico-basolateral axes. Using live imaging of endogenously tagged proteins and tissue specific protein depletion in the C. elegans embryonic intestine, we found that local and global polarity establishment are temporally and genetically separable. Local polarity is initiated prior to global polarity and is robust to perturbation. PAR-3 is required for global polarization across the intestine but is not required for local polarity establishment as small groups of cells are able to correctly establish polarized domains in PAR-3 depleted intestines in an HMR-1/E-cadherin dependent manner. Despite belonging to the same apical protein complex, we additionally find that PAR-3 and PKC-3/aPKC have distinct roles in the establishment and maintenance of local and global polarity. Together, our results indicate that different mechanisms are required for local and global polarity establishment in vivo.SUMMARY STATEMENTLive-imaging and intestine specific protein depletion reveal that apico-basolateral polarity establishment can be temporally and genetically separated at the local level of individual cells and globally, across a tissue.

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Section: Introductionmentioning

confidence: 99%

Separable mechanisms drive local and global polarity establishment in the C. elegans intestinal epithelium

Pickett

Sallee

et al. 2021

Preprint

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“…Disturbance of luminal epithelial cells' polarity and organization was reported as an early step in the breast cancer growth [39]. Moreover, loss of polarity genes such as Par3 and LKB1 was associated with highly invasive breast cancer and poor patient outcomes [40][41][42].…”

Section: B Myoepithelial Cells As Regulators Of Cellular Polaritymentioning

confidence: 99%

Re-evaluation of the myoepithelial cells roles in the breast cancer progression

Shams

2022

Cancer Cell Int

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Over the past decades, luminal epithelial cell lineage has gained considerable attraction as the functionally milk-secreting units and as the most fruitful acreage for breast cancer launching. Recognition of the effective involvement of the myoepithelial cells in mammary gland development and in hampering tumorigenesis has renewed the interest in investigating the biological roles of this second main mammary lineage. The human breast is made up of an extensively branching ductal system intervening by copious lobular units. The ductal system is coated by a chain of luminal epithelial cells (LECs) situated on a layer of myoepithelial cells (MECs) and encompassed by a distinguished basement membrane. Ductal contractility during lactation is a well-known function delivered by the MECs however this is not the only assignment mediated by these cellular populations. It has been well appreciated that the MECs exhibit a natural paracrine power in defeating cancer development and advancement. MECs were found to express numerous proteinase inhibitors, anti-angiogenic factors, and tumour suppressors proteins. Additionally, MECs contributed effectively to maintaining the right luminal cells' polarization and further separating them from the adjacent stroma by making an integrated fence. Indeed, disruption of the MECs layer was reported to facilitate the invasion of the cancer cells to the surrounding stroma. Nonetheless, MECs were also found to exhibit cancer-promoting effects and provoke tumour invasion and dissemination by displaying distinct cancer chemokines. Herein in this review, we aimed to address the roles delivered by MECs in breast cancer progression and decipher the molecular mechanisms regulating proper MECs’ physiology, integrity, and terminal differentiation. Graphical Abstract

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“…Downregulation and mislocalization of cell polarity proteins is typically observed in many human tumors (reviewed in [12]). It often appears during the early stages of malignancy [13,14] and is associated with aggressive cancers [15][16][17][18][19][20][21]. Conversely, polarity gene amplification has been reported in several human cancers.…”

Section: Loss Of the Cell Polarity Gene Scribble Triggers The Formation Of Benign Tumorsmentioning

confidence: 99%

RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

Dillard

Reis

Rusten

2021

IJMS

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The phenomenon of how oncogenes and tumor-suppressor mutations can synergize to promote tumor fitness and cancer progression can be studied in relatively simple animal model systems such as Drosophila melanogaster. Almost two decades after the landmark discovery of cooperative oncogenesis between oncogenic RasV12 and the loss of the tumor suppressor scribble in flies, this and other tumor models have provided new concepts and findings in cancer biology that has remarkable parallels and relevance to human cancer. Here we review findings using the RasV12; scrib−/− tumor model and how it has contributed to our understanding of how these initial simple genetic insults cooperate within the tumor cell to set in motion the malignant transformation program leading to tumor growth through cell growth, cell survival and proliferation, dismantling of cell–cell interactions, degradation of basement membrane and spreading to other organs. Recent findings have demonstrated that cooperativity goes beyond cell intrinsic mechanisms as the tumor interacts with the immediate cells of the microenvironment, the immune system and systemic organs to eventually facilitate malignant progression.

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Genetic alterations of epithelial polarity genes are associated with loss of polarity in invasive breast cancer

Cited by 10 publications

References 51 publications

Separable mechanisms drive local and global polarity establishment in the C. elegans intestinal epithelium

Separable mechanisms drive local and global polarity establishment in the C. elegans intestinal epithelium

Re-evaluation of the myoepithelial cells roles in the breast cancer progression

RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

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