LAMC2

LAMC2 Full Name

laminin, gamma 2

LAMC2 Introduction

The LAMC2 gene encodes the gamma-2 subunit of Laminin-332 (formerly known as Laminin-5), a heterotrimeric extracellular matrix protein essential for the cohesion of epithelial tissues. Unlike other laminin chains that are widely distributed, the gamma-2 chain is relatively restricted to the basement membranes of stratified epithelia, such as the skin and mucosa. Functionally, Laminin-332 acts as the primary "glue" that anchors basal keratinocytes to the underlying dermis via hemidesmosomes, interacting specifically with Integrin α6β4 and Integrin α3β1. However, LAMC2 is unique; it possesses a "moonlighting" function during tissue remodeling. Upon cleavage by metalloproteases (MMP-2 or MMP-14), the N-terminal fragment of the gamma-2 chain containing EGF-like repeats is released. This released fragment binds to the Epidermal Growth Factor Receptor (EGFR), triggering downstream signaling pathways that promote cell migration and scattering, rather than stable adhesion.

Figure 1. Structure of human LM 332 and its physiological maturation process. (Source: Rousselle P, et al. 2020)

The clinical relevance of LAMC2 is bifurcated into genetic deficiency and malignant overexpression. In the context of genetic disorders, loss-of-function mutations in LAMC2 result in Junctional Epidermolysis Bullosa (JEB), specifically the severe Herlitz type. Without functional gamma-2 chains, Laminin-332 cannot assemble, leading to widespread skin blistering and mucosal erosion due to the failure of epidermal-dermal adhesion. Conversely, in oncology, LAMC2 is a well-established marker of invasive carcinoma. It is frequently upregulated at the "invasive front" of tumors (such as lung, pancreatic, and squamous cell carcinomas) as part of the Epithelial-Mesenchymal Transition (EMT). The cleavage of the gamma-2 chain drives the motility of cancer cells, facilitating their detachment from the primary tumor and invasion into the surrounding stroma; thus, high LAMC2 expression is consistently associated with metastasis and poor prognosis.

Alternate Names for LAMC2

LAMC2; laminin, gamma 2; EBR2, EBR2A, LAMB2T, laminin, gamma 2 (nicein (100kD), kalinin (105kD), BM600 (100kD), Herlitz junctional epidermolysis bullosa)) , LAMNB2; laminin subunit gamma-2; BM600 100kDa; kalinin 105kDa; nicein 100kDa; BM600-100kDa; laminin B2t chain; CSF 140 kDa subunit

• 1. Rousselle P, et al. Laminin 332 in cancer: When the extracellular matrix turns signals from cell anchorage to cell movement. Semin Cancer Biol. 2020 May;62:149-165.
  2. Zhang X, et al. The multidimensional role of laminin γ2 (LAMC2) on cancer progression. Cancer Genet. 2025 Nov;298-299:122-127.