Explain the relationship between uncontrolled cell growth occurring in cancer cells and Vitamin A deficiency.

Explain the relationship between uncontrolled cell growth occurring in cancer cells and Vitamin A deficiency.

Vitamin A deficiency is not common in the US and found in those with inadequate intake (animal product, colorful vegetables, fruit), and in those at risk of fat malabsorption, and protein deficiency as with glomerular diseases of kidneys (1,2). Recognized since the time of Hippocrates, Vitamin A deficiency is classically described by the triad of:

• Xerophthalmia or abnormal dryness of eyes
• Dermatosis, such as follicular hyperkeratosis
• Night blindness (1,3)

The metabolic processes that Vitamin A participates in involve ectoderm germ layer and involve tissues related to epithelial, retina, and nervous system; however, mesodermal structures, like bone, are involved as well (3). Early studies of Vitamin A showed that its supplement to tissue cultures resulted in an increased rate of fibroblast growth, whereas to long bones its supplement was associated with inhibition of growth (3). On the reverse side, when deficient of Vitamin A, long bones developed overgrowth (3). And, with epithelial cells, vitamin A deficiency creates metaplastic results (3). Clinically, in Vitamin A deficiency, the skin becomes “rougher and more heavily cornified” and is described as hyperkeratinization (or also “toad skin”) (3). Overall with this description we sense that Vitamin A is somehow involved in ensuring that ectodermal and skeletal structures develop and differentiate properly and orderly, and when deficient there is disorderly and less well-controlled growth – this occurs with epithelial and bone tissue.
The present understanding of this elegant mechanism of action is described in Gropper’s text on page 382-3 in 7^th Edition. These mechanisms include (1):

• Inducing arrest of the cell cycle and apoptosis via stimulating a ubiquitin-proteasomal complex with insulin receptor substrate (IRS). This mechanism of cell cycle regulation occurs in hematopoietic cells, with other forms of interactions taking place in other types of tissue.
• Allowing for cell to cell signaling seems to assist with controlled cell growth. The presence of vitamin A allows for gap-junctions to form between cells, and thus improved cell to cell communication. The absence of vitamin A is associated with a lack of gap junctions and seen with uncontrolled cell growth.
• Allowing for cell “recognition, adhesion, and aggregation” the synthesis of glycoproteins on the cell surface when Vitamin A is present appears associated with proper cell growth and differentiation.

Using these mechanisms, Vitamin A plays a role in cell differentiation, and in apoptosis (cell death) which appears to provide opportunities for tissue renewal while at the same time preventing uncontrolled proliferation (1). Without this control mechanism for tissue renewal, as in Vitamin A deficiency, tissue renewal may lead to uncontrolled cell growth and possibly carcinoma (1).
Sources:
1/Gropper SS, et al. Advanced Nutrition and Human Metabolism, 7^th Ed.
2/Oregon State Universtiy, Linus Pauling Institute, Micronutrient Center, Vitamin A: https://lpi.oregonstate.edu/mic/vitamins/vitamin-A
3/Bourne DH (Ed). Biochemistry and Physiology of Nutrition, Vol 2. Academic Press, Inc, NY. 1953.