ADAM9

ADAM9 Full Name

ADAM metallopeptidase domain 9

ADAM9 Introduction

ADAM9, also known as MDC9 or meltrin γ, is a member of the ADAM (a disintegrin and metalloproteinase) family of transmembrane proteins. The gene encoding ADAM9 is located on human chromosome 8p11.22 and produces a protein of approximately 819 amino acids. Unlike some ADAM family members that have lost catalytic activity, ADAM9 possesses a functional metalloprotease domain, making it an enzymatically active sheddase. ADAM9 is widely expressed in various human tissues, including the heart, brain, lung, liver, kidney, pancreas, and placenta. It is also highly expressed in many cancer cell lines and tumor tissues. ADAM9 plays diverse roles in cell adhesion, migration, and signaling, and has been implicated in development, inflammation, and cancer progression. Its unique ability to bind integrins via its disintegrin domain and to cleave multiple cell-surface substrates positions ADAM9 as a key regulator of both physiological and pathological processes.

Figure 1.Role of ADAM9 in Protein Stabilization and Tumor Metastasis.(Lin, Yung-Wei, et al.2020)

ADAM9 in Cancer: A Pro-Tumorigenic Factor
ADAM9 is overexpressed in many human cancers, including breast cancer, prostate cancer, pancreatic cancer, lung cancer, gastric cancer, oral squamous cell carcinoma, and glioblastoma. Elevated ADAM9 expression correlates with poor prognosis, increased tumor grade, metastasis, and resistance to therapy. Mechanistically, ADAM9 promotes cancer progression through several pathways: (i) shedding of EGFR ligands (HB-EGF, amphiregulin) leading to constitutive EGFR activation; (ii) cleavage of E‑cadherin to disrupt cell‑cell adhesion and promote EMT; (iii) activation of integrin signaling via its disintegrin domain, enhancing cell migration and invasion; (iv) shedding of cell surface receptors such as CD40 to modulate immune evasion. In pancreatic cancer, ADAM9 expression is associated with desmoplasia and poor patient survival. In prostate cancer, ADAM9 promotes androgen‑independent growth and bone metastasis. These observations have made ADAM9 an attractive therapeutic target in oncology.

Role of ADAM9 in Normal Physiology and Development
Despite its pro‑tumorigenic roles in cancer, ADAM9 is essential for normal development and tissue homeostasis. ADAM9‑deficient mice are viable but exhibit mild phenotypes, including impaired angiogenesis and delayed wound healing. ADAM9 is involved in the development of the nervous system; it processes APP and may influence neurite outgrowth. In the cardiovascular system, ADAM9 contributes to angiogenesis by shedding HB‑EGF and other growth factors. In the immune system, ADAM9 regulates CD40 shedding and thus influences B‑cell activation and antibody production. Additionally, ADAM9 plays a role in sperm‑egg fusion, as it is expressed on the surface of sperm and may participate in fertilization. The relatively mild phenotype of ADAM9 knockout mice suggests that other ADAM family members may compensate for its loss, but its precise contributions to normal physiology are still being elucidated.

Alternate Names for ADAM9

ADAM9; ADAM metallopeptidase domain 9; MCMP; MDC9; CORD9; Mltng; disintegrin and metalloproteinase domain-containing protein 9; cone rod dystrophy 9; myeloma cell metalloproteinase; cellular disintegrin-related protein

• 4.Lin, Yung-Wei, et al. Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer. 2020, Cell Death & Disease,2020, 11.7: 591.