The Role of Cell Adhesion Molecule 1 (CADM1) in Cutaneous Malignancies

Abstract

Cell adhesion ability is one of the components to establish cell organization and shows a great contribution to human body construction consisting of various types of cells mixture to orchestrate tissue specific function. The cell adhesion molecule 1 (CADM1) is a molecule of cell adhesion with multiple functions and has been identified as a tumor suppressor gene. CADM1 has multifunctions on the pathogenesis of malignancies, and other normal cells such as immune cells. However, little is known about the function of CADM1 on cutaneous cells and cutaneous malignancies. CADM1 plays an important role in connecting cells with each other, contacting cells to deliver their signal, and acting as a scaffolding molecule for other immune cells to develop their immune responses. A limited number of studies reveal the contribution of CADM1 on the development of cutaneous malignancies. Solid cutaneous malignancies, such as cutaneous squamous cell carcinoma and malignant melanoma, reduce their CADM1 expression to promote the invasion and metastasis of the tumor. On the contrary to these cutaneous solid tumors except for Merkel cell carcinoma, cutaneous lymphomas, such as adult-T cell leukemia/lymphoma, mycosis fungoides, and Sézary syndrome, increase their CADM1 expression for the development of tumor environment. Based on the role of CADM1 in the etiology of tumor development, the theory of CADM1 contribution will desirably be applied to skin tumors according to other organ malignancies, however, the characteristics of skin as a multicomponent peripheral organ should be kept in mind to conclude their prognoses.

Recent Advancement in Atypical Lipomatous Tumor Research

“…These environmental stimuli provoke epigenetic changes, which regulate the biological modification of DNA without changing the sequences and subsequently influence the degree of gene expression [98]. The importance of epigenetic modification has been observed in various cutaneous skin malignancies, such as squamous cell carcinoma [99], melanoma [100], and lymphomas [101].…”

Functional and Clinical Characteristics of Cell Adhesion Molecule CADM1 in Cancer

“…Furthermore, CADM1 promotes vascular endothelial cells to repair the endothelial barrier and mast cells to release cytokines. Interestingly, high CADM1 expression in Merkel cell carcinoma, adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides, and Sezary syndrome is associated with poor prognosis (Magadmi et al, 2019;Sawada et al, 2020). However, this is contrary to previous studies that showed that CADM1 acts as a tumor suppressor in most solid tumors.…”

Cell Adhesion Molecule 1 (CADM1) Is an Independent Prognostic Factor in Patients with Cutaneous Squamous Cell Carcinoma

“…Recent studies identified that CADM1 was closely related to the development or regulation of skin cancers [9], such as SCC [25], malignant melanoma [27], adult T-cell leukemia/lymphoma [28], mycosis fungoides [17,29], Sézary Syndrome [30], and Merkel cell carcinoma [31].…”

“…The metastatic cascade is a complex multistep process, and the role of CADM1 expression is not restricted to cell-cell adhesion. However, it might also affect the infiltration of inflammatory cell migration into the tumor [9]. Indeed, CADM1 has a potent threshold for triggering the immune responses of immune cells such as NK-cell and CD8+ T-cell [40].…”

“…CADM1 belongs to the immunoglobulin superfamily, which is expressed in various normal tissues and organs including the nervous system, mast cells, testis, and lungs [7,8]. CADM1 plays an important role in suppressing malignant solid tumor cell invasion and metastasis [9]. CADM1 expression is inversely correlated with clinical stage progression, lymph node metastasis, and vascular invasion in lung cancer [10,11].…”