Cell Biology: Tissues, Cell-Matrix Adhesion, and Cancer

Vocabulary practice flashcards covering animal tissues, cell junctions, cadherin- and integrin-based cell adhesion, extracellular matrix biochemistry, and the molecular and evolutionary biology of cancer.

Epithelial Tissue

A tissue type consisting of tightly adherent, polarized cells organized into continuous sheets (which can be simple, stratified, columnar, cuboidal, or squamous) that line body cavities and surfaces, transmitting mechanical stress across cytoskeletal filaments anchored to cell-cell and cell-matrix junctions.

Connective Tissue

A tissue sparsely populated by cells (such as fibroblasts) with an extensive extracellular matrix ($\text{ECM}$) consisting of protein fibers, glycoproteins, and proteoglycans that directly bears the mechanical stresses of tension and compression.

Basal Lamina

A thin, tough extracellular mat of specialized $\text{ECM}$ directly supporting epithelial cell sheets; composed primarily of type IV collagen, laminin, perlecan, and nidogen, it acts as a selective molecular filter and a physical barrier preventing cancer cells and pathogens from invading underlying tissues.

Tight Junction (Occluding Junction)

A cell-cell sealing junction formed by transmembrane claudins and occludins that seals adjacent epithelial cells together, preventing paracellular leakage between the apical and basolateral extracellular compartments.

Gap Junction

A channel-forming junction composed of hexameric connexin complexes that align between adjacent plasma membranes to allow direct intercellular diffusion of inorganic ions and small water-soluble molecules ($< 1000\,\text{Da}$ molecular weight).

Adherens Junction

A cell-cell anchoring junction where transmembrane classical cadherins link neighboring cells together and connect to circumferential cortical actin filament bundles (adhesion belts) via intracellular adaptor proteins including $\alpha$-catenin, $\beta$-catenin, and vinculin.

Desmosome

A button-like cell-cell anchoring junction that links intermediate filaments (such as keratin) between adjacent cells via nonclassical cadherin family members (desmoglein and desmocollin) and cytoplasmic plaque adaptors (plakoglobin, plakophilin, and desmoplakin).

Hemidesmosome

A specialized cell-matrix anchoring junction that anchors the intermediate filament cytoskeleton (keratin) of an epithelial cell to the basal lamina using transmembrane $\alpha_6\beta_4$ integrin and type XVII collagen, bound intracellularly via plectin and BP230.

Actin-Linked Cell-Matrix Junction (Focal Adhesion)

An integrin-based anchoring complex that fastens intracellular actin filaments (stress fibers) to extracellular matrix proteins via cytoplasmic adaptor and signaling proteins including talin, vinculin, kindlin, paxillin, and focal adhesion kinase (FAK).

Cadherin

A family of $\text{Ca}^{2+}$-dependent transmembrane adhesion proteins whose extracellular repeating domains bind homophilically to cadherins on neighboring cells; binding requires $\text{Ca}^{2+}$ ($> 1\,\text{mM}$ maintains a rigid, extended conformation, whereas $< 0.05\,\text{mM}$ causes floppy domains and loss of adhesion).

Mechanotransduction in Adherens Junctions

The mechanism whereby tension applied by non-muscle myosin II pulling on junctional actin filaments physically unfolds a domain within $\alpha$-catenin, exposing a hidden binding site that recruits vinculin to capture more actin filaments and reinforce the junction.

Cell Sorting

The spatial segregation and aggregation of mixed cell populations during embryonic development driven by differences in the type (e.g., E-cadherin vs. N-cadherin during neural tube formation) or expression level of cadherin molecules on the cell surface.

Collagen

The major fibrous protein of animal extracellular matrix consisting of a three-stranded triple helix characterized by a repeating $\text{Gly-Pro-}X$ amino acid motif; glycine occurs at every third position because its hydrogen side chain is the only one small enough to fit inside the crowded center of the helix.

Procollagen

A soluble biosynthetic precursor of collagen synthesized with terminal non-helical propeptides that prevent premature intracellular fibril assembly; after secretion via exocytosis, extracellular enzymes cleave the propeptides, initiating spontaneous self-assembly into collagen fibrils.

Type I Collagen

The most abundant fibril-forming collagen in vertebrates (constituting $90\%$ of body collagen) found in bone, skin, tendons, ligaments, and cornea; mutations in its genes result in osteogenesis imperfecta (severe bone defects and fractures).

Type IV Collagen

A network-forming collagen found specifically in the basal lamina that polymerizes into a flexible, sheet-like meshwork providing mechanical support and filtration functions; mutations cause glomerulonephritis and hereditary deafness.

Fibronectin

A large extracellular matrix glycoprotein consisting of two disulfide-linked subunits that possesses multiple discrete binding domains for collagen, heparin, and integrin receptors, helping organize matrix assembly and cell attachment.

RGD Sequence

A specific tripeptide sequence (Arginine-Glycine-Aspartate) found within fibronectin and other $\text{ECM}$ proteins that serves as the primary recognition motif for several integrin receptors; synthetic soluble RGD peptides can competitively inhibit cell-matrix binding.

Integrin

A family of obligate heterodimeric transmembrane adhesion receptors consisting of noncovalently linked $\alpha$ and $\beta$ subunits (18 $\alpha$ and 8 $\beta$ subunits in humans) that mediate bidirectional signaling (inside-out and outside-in) by transitioning between bent inactive and extended active conformations.

Talin

A major focal adhesion adaptor protein whose N-terminal FERM head domain binds the cytoplasmic tail of $\beta$-integrins to activate them, while its flexible C-terminal rod domain contains up to 11 cryptic vinculin-binding sites that unfold under mechanical cytoskeletal tension.

Architecture of Focal Adhesions

The nanoscale vertical organization of focal adhesions into three distinct functional strata: the Integrin Signaling Layer ($\sim 20\,\text{nm}$, containing integrin tails, talin head, FAK, and paxillin), the Force Transduction Layer ($\sim 20\,\text{nm}$, containing the talin rod and vinculin), and the Actin Regulatory Layer ($\sim 60\,\text{nm}$, containing actin, $\alpha$-actinin, and Arp2/3).

Junctional Epidermolysis Bullosa

A severe genetic disorder characterized by extensive skin and mucosal blistering, caused by loss-of-function mutations in hemidesmosome structural components including $\alpha_6$ or $\beta_4$ integrin subunits, type XVII collagen, or laminin.

Cell Number Homeostasis

The physiological balance that maintains normal tissue size by equilibrating cell proliferation (driven by growth factors and cell cycle promoters, restrained by checkpoints and inhibitors) with cell death (driven by death signals and damage, restrained by survival factors and apoptosis inhibitors).

Hallmarks of Cancer

A set of distinctive functional capabilities acquired by human cells during multi-step tumorigenesis, including sustained proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming cell energetics, avoiding immune destruction, tumor-promoting inflammation, and genome instability.

Contact Inhibition of Proliferation

The normal homeostatic phenomenon whereby monolayer cultured cells cease cell division upon reaching confluence through homophilic E-cadherin interactions; cancer cells lose contact inhibition, continuing division to pile up into multilayered foci.

Proto-Oncogene

A normal cellular gene promoting cell survival or cell cycle progression that, upon receiving a gain-of-function (dominant/hypermorphic) mutation in a single allele, converts into a hyperactive oncogene driving unchecked tumorigenesis (e.g., Ras, EGFR).

Tumor Suppressor Gene

A gene that normally restrains cell division or promotes repair and apoptosis; cancer mutations in these genes are functionally recessive, requiring two-copy (biallelic) loss-of-function inactivation in a single cell lineage to release negative growth control (e.g., TP53, RB1).

Philadelphia Chromosome

An abnormally shortened chromosome 22 ($\text{Ph } 22\text{q}-$) resulting from a reciprocal chromosomal translocation with chromosome 9, $t(9; 22)$, creating an oncogenic $BCR\text{-}ABL$ fusion gene encoding a hyperactive, constitutively active tyrosine kinase that causes chronic myelogenous leukemia ($\text{CML}$).

Gleevec (Imatinib)

A targeted small-molecule therapeutic drug designed to fit into the ATP-binding pocket of the hyperactive oncogenic BCR-Abl tyrosine kinase, blocking ATP binding and preventing substrate phosphorylation to treat chronic myelogenous leukemia ($\text{CML}$) and gastrointestinal stromal tumors ($\text{GIST}$).

Colorectal Carcinoma Progression Model

The classical multi-step genetic paradigm of tumor progression where normal intestinal epithelium undergoes successive mutations: loss of APC (hyperplastic epithelium to early adenoma), activation of K-Ras (intermediate adenoma), loss of Smad4 (late adenoma), and loss of p53 (invasive carcinoma).

Metastasis

The multi-step spread of malignant cancer cells from a primary tumor through blood or lymphatic vessels to colonize distant tissues; responsible for approximately $2/3$ of cancer deaths, despite fewer than $1\text{ in } 1000$ circulating cancer cells surviving to form distant metastases.