Trends in Cell Biology
ReviewSpecial Issue: Cell Biology of CancerIntegrins and cancer: regulators of cancer stemness, metastasis, and drug resistance
Section snippets
Integrin heterodimers and ligand specificity in cancer
When the extracellular matrix (ECM) is proteolytically degraded or deformed by mechanical forces, cells are prompted to undergo responsive changes that influence remodeling during physiological and pathological events. Integrins are a family of heterodimeric cell surface receptors that sense these changes and trigger a range of cellular responses by forming a physical connection between the inside and outside of a cell to allow the bidirectional ‘integration’ of signals to control cell
Dissecting integrin-dependent regulation of stem cells
Although epithelial stem cells play a critical role in the physiological development, maintenance, and remodeling of organs and tissues [17], their properties are also associated with the initiation and progression of carcinomas [18]. Since the stem cell niche is tightly regulated by signals from the local microenvironment including the ECM, certain integrins may be critical for the ability of stem cells to sense and respond to these cues in both normal tissues and cancer. Indeed, a number of
Connecting integrins and drug resistance
Despite advances in cancer treatment, many cancer therapies are limited by the development of resistance that results from a variety of factors, including alterations in the drug target, activation of prosurvival pathways, and ineffective induction of cell death. Resistance to anticancer therapeutics can be divided into two categories: intrinsic resistance derived from genetic or environmental factors pre-existing in the tumor, or acquired resistance resulting from adaptive responses,
Critical roles for integrins during the metastatic cascade
Metastasis is a multistep process that requires a cancer cell to escape from the primary tumor, survive in the circulation, colonize distant sites, and proliferate. Since integrin function can enable and enhance many facets of these steps, it is not surprising that increased expression of certain integrins within the primary tumor are associated with poor prognosis and enhanced metastasis in a variety of cancers [1] (Figure 3). This increased expression may reflect higher numbers of CSCs with
Concluding remarks
Recent findings have demonstrated that integrins participate in the regulation of stem-cell and cancer stem-cell biology and are required for cancer progression and drug resistance (Figure 3). Further understanding of which specific integrins are required for these events, whether these integrins are interchangeable or specifically required, whether these integrins define a subset of cells that expand in response to changes in the microenvironment, or whether a dynamic program allows the cells
References (66)
Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3
Cell
(1996)CD151 in cancer progression and metastasis: a complex scenario
Lab. Invest.
(2014)- et al.
Cancer stem cells: current status and evolving complexities
Cell Stem Cell
(2012) The basement membrane of hair follicle stem cells is a muscle cell niche
Cell
(2011)MT1-MMP-dependent control of skeletal stem cell commitment via a beta1-integrin/YAP/TAZ signaling axis
Dev. Cell
(2013)The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells
Cell Stem Cell
(2012)A role for matrix metalloproteinases in regulating mammary stem cell function via the Wnt signaling pathway
Cell Stem Cell
(2013)Integrin alphavbeta3 drives slug activation and stemness in the pregnant and neoplastic mammary gland
Dev. Cell
(2014)A rare population of CD24(+)ITGB4(+)Notch(hi) cells drives tumor propagation in NSCLC and requires Notch3 for self-renewal
Cancer Cell
(2013)Integrin alpha 6 regulates glioblastoma stem cells
Cell Stem Cell
(2010)
Regulated splicing of the alpha6 integrin cytoplasmic domain determines the fate of breast cancer stem cells
Cell Rep.
Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion
Cancer Cell
beta1 integrin is required for anchorage-independent growth and invasion of tumor cells in a context dependent manner
Cancer Lett.
Targeting tumor-stromal interactions in bone metastasis
Pharmacol. Ther.
Integrins in cancer: biological implications and therapeutic opportunities
Nat. Rev. Cancer
Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression
Nat. Med.
The final steps of integrin activation: the end game
Nat. Rev. Mol. Cell Biol.
Integrins
Cell Tissue. Res.
EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation
Oncogene
Enhancing integrin function by VEGF/neuropilin signaling: implications for tumor biology
Cell Adhes. Migrat.
Differential alphav integrin-mediated Ras-ERK signaling during two pathways of angiogenesis
J. Cell Biol.
Integrin signalling during tumour progression
Nat. Rev. Mol. Cell Biol.
Integrin cytoplasmic tail interactions
Biochemistry
A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis
Nat. Commun.
Galectin-1 promotes lung cancer tumor metastasis by potentiating integrin alpha6beta4 and Notch1/Jagged2 signaling pathway
Carcinogenesis
An integrin beta(3)-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition
Nat. Cell Biol.
Tetraspanins at a glance
J. Cell Sci.
Tspan8, CD44v6 and alpha6beta4 are biomarkers of migrating pancreatic cancer-initiating cells
Int. J. Cancer
Stem cell plasticity. Plasticity of epithelial stem cells in tissue regeneration
Science
Interactions between cancer stem cells and their niche govern metastatic colonization
Nature
Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs
Nat. Med.
Beta1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells
Nat. Cell Biol.
Kindlin-1 controls Wnt and TGF-beta availability to regulate cutaneous stem cell proliferation
Nat. Med.
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