Cystathione β-Synthase Is Increased in Thyroid Malignancies

Abstract

Background: Cystathione β-synthase (CBS) catalyzes the conversion of homocysteine and cysteine to hydrogen sulfide (H 2 S) and cystathione, via the transsulfuration pathway. CBS protein expression levels are increased in several different human malignancies, with increased protein expression correlating with parameters such as tumor stage, anaplasia, metastases, and chemotherapy resistance. Materials and Methods: This study employed tissue microarrays to examine CBS expression in benign thyroid tissue, thyroid oncocytomas, thyroid follicular adenomas, and in follicular, papillary, anaplastic, and medullary thyroid carcinomas. Results: CBS expression was increased in all thyroid carcinomas types compared to benign thyroid tissue, but not in thyroid follicular adenomas or oncocytomas. A similar pattern was observed for nicotinamide phosphoribosyltransferase (NAMPT) tissue microarray analysis comparing thyroid adenomas and follicular carcinomas. Conclusion: For the first time, we showed that an H 2 S-syntheszing enzyme plays a role in thyroid malignancies. Additionally, our data suggest that CBS and NAMPT immunohistochemistry may be useful in differentiating follicular adenomas from follicular carcinomas.

Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis

“…Endogenous H 2 S derived from these three enzymes plays an influential role on tumor growth in a variety of different cancer types through induction of angiogenesis, regulation of mitochondrial bioenergetics, acceleration of cell cycle progression, and anti-apoptosis [16]. Among them, CBS was upregulated in thyroid [17], ovarian [18], and colon cancers [19,20], while CTH promoted cell growth in breast cancer cells [21] and astrocytoma cells [22]. Increased expressions of 3MST were observed in colon, lung adenocarcinoma, urothelial cell carcinoma, and oral carcinomas, implying that 3MST may play a role in drug resistance and oxidative damage during cancer progression [23].…”

Cysteine metabolic circuitries: druggable targets in cancer

“…Given the increased expression of cysteine catabolic enzymes, such as cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-MST in different cancer cell types, it is likely that their relevance for cancer development is shared between the production of H 2 S (detailed later in the article) and the accompanying generation of metabolites that constitute carbon sources. [52][53][54][55][56][57][58][59][60] Fig . 1 Cysteine metabolic fate.…”

The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

“…CBS, which catalyzes H 2 S by driving beta-replacement, has been observed to be selectively upregulated in colon cancer, ovarian cancer, breast cancer, thyroid cancer, and gallbladder adenocarcinoma tissues [ 57 , 60 , 61 , 73 ]. CBS is a constitutively expressed enzyme and its activity can be regulated post-translationally [ 74 ].…”