Emerging role of cell polarity proteins in breast cancer progression and metastasis

Figures & data

Figure 1 Breast tumor progression.

Note: Cross-section of a duct shows loss of epithelial integrity and ductal filling across the different stages of breast cancer.

Figure 2 Polarity complexes in epithelial cells.

Notes: The localization of the Crumbs, Par, and Scribble complexes define the apical and basolateral domains through complex interactions and mutual exclusion.
Abbreviations: Amot, angiomotin; aPKC, atypical protein kinase C; cdc42, cell division control protein 42; Crb, Crumbs 3; Dlg, Discs-large; Lgl, lethal giant larvae; Lkb1, liver kinase b1; Patj, Pals1-associated tight junction protein; Scrib, Scribble.

Figure 3 Potential mechanisms by which normal epithelial organization can be lost early in the progression of breast cancer.

Notes: The model on the left shows a cell undergoing EMT to migrate out of the epithelial plane, then reverting through a MET. In the middle model, the epithelial cells rearrange so that they are multilayered. The model at the right shows a cell division perpendicular to the epithelial plane would give rise to a multilayered duct.
Abbreviations: EMT, epithelial-mesenchymal transition; MET, mesenchymal-epithelial transition.

Figure 4 Model for oriented cell division.

Note: Members of the Par complex and Dlg interact with LGN to anchor spindle poles to the lateral membranes.
Abbreviations: aPKC, atypical protein kinase C; cdc42, cell division control protein 42; Dlg, Discs-large; E-cad, E-cadherin; LGN, Leu-Gly-Asn repeat-enriched protein; NuMA, nuclear mitotic apparatus protein; MT, microtubule; Gαi, guanine nucleotide binding protein alpha inhibitory 1.

Figure 5 Signaling pathways regulated by apical–basal polarity complexes.

Notes: The polarity complexes impinge upon different signaling pathways. Loss or disruption of normal function of polarity proteins during tumorigenesis correspondingly deregulates the normal function of these pathways and processes, by stimulating their activation or inhibiting them.
Abbreviations: Bim, Bcl-2 interacting mediator of cell death; Crb, Crumbs 3; c-Jun, cellular Jun; ECM, extracellular matrix; HER2, human epidermal growth factor receptor 2; Jak, Janus kinase; JNK, c-Jun N-terminal kinase; Lkb1, liver kinase b1; MAPK, mitogen activated protein kinase; MMP, matrix metalloproteinase; PI3K, phosphatidylinositide 3-kinase; RhoA, Ras homolog gene family member A; Scrib, Scribble; Stat, signal transducer and activator of transcription; TGF, transforming growth factor.

Figure 6 Regulation of Hippo-Yap1/Taz signaling by polarity complexes. The apical Crumbs and lateral Scrib complexes can sequester Yap1/Taz and the Hippo pathway kinases to prevent proliferation in polarized epithelial cells (left). Loss of polarity inactivates the Hippo pathway and releases Yap1/Taz to enter the nucleus to regulate proliferation (right). The Crumbs complex can also regulate SMADs to sensitize cells to epithelial-mesenchymal transition.

Abbreviations: Amot, angiomotin; Crb, Crumbs; EMT, epithelial-mesenchymal transition; Lats, large tumor suppressor; Mst, mammalian STE20-like protein kinase; NF, neurofibromin 2; Patj, Pals1-associated tight junction protein; Scrib, Scribble; Taz, transcriptional coactivator with PDZ binding motif; Yap, Yes-associated protein.